Publications by authors named "Elina Toskala"

70 Publications

Assessment of narcotic use in management of post-op pain after functional endoscopic sinus surgery.

Laryngoscope Investig Otolaryngol 2021 Feb 9;6(1):42-48. Epub 2021 Jan 9.

Department of Otolaryngology-Head & Neck Surgery Thomas Jefferson University Hospital Philadelphia Pennsylvania USA.

Objectives: Pain and analgesic requirements after functional endoscopic sinus surgery (FESS) vary widely. This study aims to quantify pain after routine FESS and determine the most commonly used pain management regimen.

Methods: Retrospective chart review of 100 patients who underwent FESS from Oct 2017 to May 2019. Patients prospectively completed a daily pain diary and reported pain levels that were categorized into no pain (0), mild (1-3), moderate (4-7), or severe (8-10). Patients were categorized into narcotics, non-narcotics, combination, or none based on type of analgesic used.

Results: Sixty-nine patients were included. Majority of patients reported either mild (39%) or no pain (28%) during the first 5 PODs. Mean POD1 pain score was 3.98, which decreased with each subsequent POD. On POD1, 37% used opioids (n = 37), 32% used non-opioids (n = 32), 22% used a combination (n = 22), and 9% used no pain meds (n = 9). Mean number of narcotic pills used within the first 5 PODs was 2 pills on any given day. Age was inversely associated with reported POD1 pain scores ( = .003) and use of preoperative steroids in patients with sinonasal polyposis was associated with lower POD1 pain scores ( = .03).

Conclusions: Even on POD1, majority of patients experienced either mild or no pain, and this decreases with each POD. Narcotics are grossly overprescribed and underutilized by patients postoperatively after FESS. We advocate for more judicious prescribing habits of narcotics by Otolaryngologists after FESS, and emphasize relying on non-narcotic alternatives like Acetaminophen or NSAIDS to diminish narcotic use and abuse in the postoperative period.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lio2.519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883617PMC
February 2021

Free tissue transfer for central skull base defect reconstruction: Case series and surgical technique.

Oral Oncol 2021 Apr 13;115:105220. Epub 2021 Feb 13.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, United States. Electronic address:

Objectives: Local reconstruction of central skull base defects may be inadequate for large defects or reoperative cases; free tissue transfer may be necessary. Inset of the flap and management of the pedicle can be challenging. We report our experience and approaches.

Methods: Retrospective review identifying seven patients with central skull base defects who underwent free flap reconstruction from 2016 to 2020.

Results: Four patients with recurrent nasopharyngeal carcinoma, one with recurrent craniopharyngioma, one with clival-cervical chordoma, and one with meningioma of the middle cranial fossa were analyzed. Six defects were closed with an anterolateral thigh free flap and one with a radial forearm free flap. In two patients, the flap was secured in an onlay fashion to the defect via a Caldwell-Luc transmaxillary approach. In one patient, the flap was passed transorally, and the pedicle was delivered into the neck via Penrose drain. In two patients, a parapharyngeal technique and in two others, a retropharyngeal was used for nasopharyngeal inset with endoscopic assistance. There were no flap failures, with an average follow-up time of 20.1 (range 3.2-47.1) months. One patient required flap repositioning on postoperative day three due to midline shift and intracranial contents compression. The transoral inset flap necessitated flap repositioning on postoperative day 13 to improve the nasopharyngeal airway.

Conclusion: Free flap reconstruction of the central skull base is challenging, but transmaxillary, transoral, parapharyngeal, and retropharyngeal approaches can be used with endoscopic assistance to ensure secure inset flap and avoid airway obstruction.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105220DOI Listing
April 2021

Quality of Life Outcomes in Patients With Sinonasal Malignancy After Definitive Treatment.

Laryngoscope 2020 Dec 25. Epub 2020 Dec 25.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: To describe multidimensional quality of life (QOL) outcomes in patients with sinonasal malignancies (SNM). To elucidate factors predicting worse QOL in this population.

Study Design: Retrospective chart review at tertiary institution.

Methods: A retrospective chart review on patients treated for SNM from 2006 to 2019 at a tertiary medical center was conducted. QOL outcomes were measured using the Hospital Anxiety and Depression Scale (HADS) and the Functional Assessment Cancer Therapy - Nasopharynx (FACT-NP) score. A stepwise multiple linear regression analysis was conducted to assess factors predicting worse QOL.

Results: Eighty-one patients met inclusion criteria. Twelve (14.8%) patients had a subscale score >11 for anxiety (HADS-A) or depression (HADS-D) indicating significant anxiety or depression, at a median of 24 (8-68.5) months post treatment. The median FACT-NP total score was 136 (110-152). On multivariable analysis, advanced T classification, single status, and worse social support survey score were significant predictors of worse HADS score. Worse social support survey score was a significant predictor of worse total FACT-NP score.

Conclusion: After adjusting for confounders, at a median of 24 months after completion of definitive therapy for SNM, advanced T classification and single relationship status were found to be significant predictors of anxiety and depression (based on HADS). A worse social support survey score was associated with worse anxiety, depression, and QOL (based on HADS and FACT-NP). Identifying these factors early may help to guide treatment and psychiatric referral to at-risk individuals after the treatment of SNM.

Level Of Evidence: 3. Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.29339DOI Listing
December 2020

Effect of Benralizumab in Patients With Severe Eosinophilic Asthma and Chronic Rhinosinusitis With Nasal Polyps: A Case Series.

Am J Rhinol Allergy 2020 Dec 10:1945892420978351. Epub 2020 Dec 10.

Department of Pulmonology and Respiratory Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

Objective: To analyze the effect of benralizumab in severe eosinophilic asthma (SA) and chronic rhinosinusitis with polyps (CRSwP).

Methods: Retrospective review of patients with SA and CRSwP that were treated with benralizumab. Asthma controlled test (ACT), pulmonary function metrics (FEV1), Meltzer endoscopic polyp scores, SNOT-22 scores, were collected before and after at least 4 months of benralizumab therapy.

Results: 23 patients were included. The mean age at the time of enrollment into benralizumab therapy was 50.47 ± 17.3 years and majority (65.2%, n = 15) were males.Pulmonary Effects: In comparison to baseline ACT, scores at four months showed significant improvement (p = 0.03). In those with pre and post spirometry measurements, mean FEV1 showed significant increase following benralizumab therapy (p = 0.04) with a mean increase of 547 mL ± 597 mL following therapy.Sinonasal Effects: 78.5% of subjects on benralizumab had a significant improvement in sinonasal symptoms (p = 0.009) based on their SNOT-22 scores. Additionally, there was an improvement in endoscopic polyp scores, although not statistically significant, following benralizumab therapy (p = 0.2) with 54.5% patients showing improvement.

Conclusion: Usage of benralizumab in patients with SA and CRSwNP can lead to significantly improved asthma control, lung function, and sinonasal quality of life. Additionally, in this patient population, there was a subset of patients that showed a significant reduction in polyp burden.
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http://dx.doi.org/10.1177/1945892420978351DOI Listing
December 2020

Preoperative Screening for Obstructive Sleep Apnea Prior to Endoscopic Skull Base Surgery: A Survey of the North American Skull Base Society.

Allergy Rhinol (Providence) 2020 Jan-Dec;11:2152656720968801. Epub 2020 Nov 12.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

Background: Obstructive sleep apnea (OSA) is a commonly seen comorbidity in patients undergoing endoscopic skull base surgery and its presence may influence perioperative decision-making. Current practice patterns for preoperative screening of OSA are poorly understood.

Objective: The objective of this study was to assess how endoscopic skull base surgeons screen for OSA, and how knowledge of OSA affects perioperative decision-making.

Methods: Seven question survey distributed to members of the North American Skull Base Society.

Results: Eighty-eight responses (10% response rate) were received. 60% of respondents were from academic centers who personally performed >50 cases per year. Most respondents noted that preoperative knowledge of OSA and its severity affected postoperative care and increased their concern for complications. Half of respondents noted that preoperative knowledge of OSA and its severity affects intraoperative skull base reconstruction decision-making. 70% of respondents did not have a preoperative OSA screening protocol. Body mass index and patient history were most frequently used by those who screened. Validated screening questionnaires were rarely used. 76% of respondents agreed or somewhat agreed that a preoperative polysomnogram should ideally be performed for patients with suspected OSA; however, 50% of respondents reported that <20% of their patients with suspected OSA are advised to obtain a preoperative polysomnogram.

Conclusion: This study reveals that most endoscopic skull base surgeons agree that OSA affects postoperative patient care, but only a minority have a preoperative screening protocol in place. Additional study is needed to assess the most appropriate screening methods and protocols for OSA patients undergoing endoscopic skull base surgery.
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http://dx.doi.org/10.1177/2152656720968801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672726PMC
November 2020

Guidance for contemporary use of biologics in management of chronic rhinosinusitis with nasal polyps: discussion from a National Institutes of Health-sponsored workshop.

Int Forum Allergy Rhinol 2020 Sep 3;10(9):1037-1042. Epub 2020 Jul 3.

Department of Otolaryngology, Head and Neck Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX.

Background: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness.

Methods: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients.

Results: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice.

Conclusion: We suggest that physicians evaluate patients on an individual basis and closely monitor for improvement due to the high cost and unknown long-term effects of biologics.
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http://dx.doi.org/10.1002/alr.22633DOI Listing
September 2020

Clinical Research Needs for the Management of Chronic Rhinosinusitis with Nasal Polyps in the New Era of Biologics: A National Institute of Allergy and Infectious Diseases Workshop.

J Allergy Clin Immunol Pract 2020 05 4;8(5):1532-1549.e1. Epub 2020 Mar 4.

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address:

The development of biologics targeting various aspects of type 2 inflammation for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) will provide clinicians with powerful tools to help treat these patients. However, other therapies are also available, and positioning of biologics in a management algorithm will require comparative trials. In November 2019, the National Institute of Allergy and Infectious Diseases convened a workshop to consider potential future trial designs. Workshop participants represented a wide spectrum of clinical specialties, including otolaryngology, allergy, and pulmonary medicine, as well as expertise in CRSwNP pathophysiology and in trial methodology and statistics. The workshop discussed the current state of knowledge in CRSwNP and considered the advantages and disadvantages of various clinical trial or observational study designs and various clinical outcomes. The output from this workshop, which is presented in this report, will hopefully provide investigators with adequate information and ideas to design future studies and answer critical clinical questions. It will also help clinicians understand the current state of the management of CRSwNP and its gaps and be more able to interpret the new information to come.
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http://dx.doi.org/10.1016/j.jaip.2020.02.023DOI Listing
May 2020

Evolution in the surgical management of chronic rhinosinusitis: Current indications and pitfalls.

J Allergy Clin Immunol 2018 05 29;141(5):1561-1569. Epub 2018 Mar 29.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pa. Electronic address:

Chronic rhinosinusitis (CRS) consists of a range of inflammatory conditions in the sinuses that can result in clinical symptoms. The underlying pathophysiology and its relationship to lower airway disease are complex. Current definitions of CRS can serve more as an indication for potential surgical intervention rather than a marker of disease state. CRS can be asymptomatic and may require medical management to avoid disease progression and minimize the risk of lower airway disease. Endoscopic surgery has undergone a significant evolution and refinement, but the most common surgical complication remains persistent inflammation and disease recurrence. It is important to recognize that surgery alone rarely cures CRS and patients require long-term medical therapy for continued asymptomatic inflammation. Careful postoperative care and endoscopic follow-up to ensure resolution of inflammation are key to ensuring optimal surgical outcomes and reduce the risk of revision surgery. Future work on CRS endotypes will allow discovery of new therapies to treat CRS, as well as refine indications for medical or surgical intervention and postoperative care.
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http://dx.doi.org/10.1016/j.jaci.2018.03.003DOI Listing
May 2018

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis.

Int Forum Allergy Rhinol 2018 02;8(2):108-352

Otolaryngology, University of Michigan, USA.

Background: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).

Methods: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.

Results: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR.

Conclusion: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.
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http://dx.doi.org/10.1002/alr.22073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286723PMC
February 2018

International consensus statement on allergy and rhinology: allergic rhinitis-executive summary.

Int Forum Allergy Rhinol 2018 02;8(2):85-107

Department of Otolaryngology-Head and Neck Surgery, Temple University, Philadelphia, PA.

Background: The available allergic rhinitis (AR) literature continues to grow. Critical evaluation and understanding of this literature is important to appropriately utilize this knowledge in the care of AR patients. The International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) has been produced as a multidisciplinary international effort. This Executive Summary highlights and summarizes the findings of the comprehensive ICAR:AR document.

Methods: The ICAR:AR document was produced using previously described methodology. Specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.

Results: Over 100 individual topics related to AR diagnosis, pathophysiology, epidemiology, disease burden, risk factors, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR were addressed in the comprehensive ICAR:AR document. Herein, the Executive Summary provides a synopsis of these findings.

Conclusion: In the ICAR:AR critical review of the literature, several strengths were identified. In addition, significant knowledge gaps exist in the AR literature where current practice is not based on the best quality evidence; these should be seen as opportunities for additional research. The ICAR:AR document evaluates the strengths and weaknesses of the AR literature. This Executive Summary condenses these findings into a short summary. The reader is also encouraged to consult the comprehensive ICAR:AR document for a thorough description of this work.
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http://dx.doi.org/10.1002/alr.22070DOI Listing
February 2018

Manifestations of Inhalant Allergies Beyond the Nose.

Otolaryngol Clin North Am 2017 Dec 28;50(6):1051-1064. Epub 2017 Sep 28.

Department of Otolaryngology-Head and Neck Surgery, Lewis Katz School of Medicine at Temple University, 3440 North Broad Street, Kresge West 312, Philadelphia, PA 19140, USA. Electronic address:

The upper and lower airways are linked epidemiologically and pathophysiologically. The upper and lower airways are considered a single, functional unit characterized by shared immunologic mechanisms, often referred to as the unified airway. Upper and lower airway inflammatory disease frequently coexist in the same patient. Allergic rhinitis and rhinosinusitis are associated with asthma. Treatment of both diseases impacts asthma outcomes. The otolaryngologist may be the first physician to suspect and diagnose asthma in patients with upper airway complaints. A thorough understanding of the relationship between allergic rhinitis, rhinosinusitis, and asthma will facilitate early identification of asthma and improve patient outcomes.
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http://dx.doi.org/10.1016/j.otc.2017.08.004DOI Listing
December 2017

Editorial.

Authors:
Elina Toskala

Int Forum Allergy Rhinol 2017 05;7(5):439-440

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http://dx.doi.org/10.1002/alr.21947DOI Listing
May 2017

Airborne Particulate Matter Induces Nonallergic Eosinophilic Sinonasal Inflammation in Mice.

Am J Respir Cell Mol Biol 2017 07;57(1):59-65

2 Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 μm) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 μm/m, a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin-1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL-13, eotaxin-1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.
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http://dx.doi.org/10.1165/rcmb.2016-0351OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516278PMC
July 2017

Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.

J Allergy Clin Immunol 2016 05 4;137(5):1449-1456.e4. Epub 2016 Mar 4.

Upper Airways Research Laboratory, Ghent University, Ghent, Belgium; Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Background: Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS.

Objective: We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes.

Methods: In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering.

Results: Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a TH17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE.

Conclusion: Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.
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http://dx.doi.org/10.1016/j.jaci.2015.12.1324DOI Listing
May 2016

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis.

Int Forum Allergy Rhinol 2016 Feb;6 Suppl 1:S22-209

University of Pennsylvania.

Background: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS).

Methods: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus.

Results: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS.

Conclusion: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.
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http://dx.doi.org/10.1002/alr.21695DOI Listing
February 2016

Risk Factors and Comorbidities in Chronic Rhinosinusitis.

Curr Allergy Asthma Rep 2016 Feb;16(2):16

Temple Head & Neck Institute, 3440 N. Broad Street, Kresge West 3rd Floor, Philadelphia, PA, 19140, USA.

Chronic rhinosinusitis (CRS) is a heterogeneous disorder that creates a significant burden on the healthcare system. It is caused by a combination of inflammatory, environmental, and host factors; however, the precise mechanism of how each factor leads to CRS continues to be a source of debate. Previous data regarding this topic is often inconsistent or of lower quality. In this article, we review the recent literature on the risk factors and comorbidities in CRS. Large population-based studies have helped establish smoking as a significant risk factor for CRS. The focus has now shifted towards smoking and its effect on long-term outcomes after endoscopic sinus surgery (ESS). Ciliary dyskinesia, both primary and secondary, can affect both the sinonasal cavity and lower airways simultaneously by decreasing the beat frequency of cilia and inducing mucostasis. The effects of secondary dyskinesia may be reversible and there is some evidence to suggest the use of topical mucolytics in patients with CRS. Allergy and variants of sinonasal anatomy have been hypothesized to increase the risk of developing CRS by inducing chronic inflammation and obstructing the sinus ostia. Nevertheless, emerging data regarding these topics continue to produce inconclusive results. Inflammation of the upper and lower airways can occur simultaneously as seen in patients with asthma and aspirin sensitivity. The connection between these pro-inflammatory disease states has been known for many years. Newer evidence include large population-based studies and studies that correlate objective tests, such as computer tomography scans to pulmonary function tests. However, the treatment of CRS and its effects on obstructive airway disease continues to be a topic of debate. More large prospective studies are needed in order to continue refining our knowledge of the disease processes in CRS.
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http://dx.doi.org/10.1007/s11882-015-0589-yDOI Listing
February 2016

Meta-analysis identifies seven susceptibility loci involved in the atopic march.

Nat Commun 2015 Nov 6;6:8804. Epub 2015 Nov 6.

Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany.

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
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http://dx.doi.org/10.1038/ncomms9804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667629PMC
November 2015

Asthma risk factors.

Int Forum Allergy Rhinol 2015 Sep;5 Suppl 1:S11-6

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Background: Bronchial asthma is one of the most common chronic diseases in childhood, with a current prevalence of 6% to 9%, but a prevalence that is increasing at an alarming rate. Asthma is a complex genetic disorder with strong environmental influence. It imposes a growing burden on our society in terms of morbidity, quality of life, and healthcare costs. Despite large-scale efforts, only a few asthma genes have been confirmed, suggesting that the genetic underpinning of asthma is highly complex.

Methods: A review of the literature was performed regarding atopic and nonatopic asthma risk factors, including environmental risk factors and genetic studies in adults and children.

Results: Several environmental risk factors have been identified to increase the risk of developing asthma such as exposure to air pollution and tobaccos smoke as well as occupational risk factors. In addition atopy, stress, and obesity all can increases the risk for asthma in genetically susceptible persons.

Conclusion: Asthma represents a dysfunctional interaction with our genes and the environment to which they are exposed, especially in fetal and early infant life. The increasing prevalence of asthma in all age groups indicate that our living environment and immunity are in imbalance with each other reacting with airway inflammation to the environmental exposures and often non-harmful proteins, such as allergens causing the current "asthma and allergy epidemic." Because of the close relationship between asthma and chronic rhinosinusitis, it is important that otolaryngologists have a good understanding of asthma, the etiologic factors associated with disease, and its evaluation and management.
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http://dx.doi.org/10.1002/alr.21557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159773PMC
September 2015

Dosing of sublingual immunotherapy for allergic rhinitis: evidence-based review with recommendations.

Int Forum Allergy Rhinol 2015 Sep 11;5(9):773-83. Epub 2015 Jun 11.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD.

Background: Since the mid 1980s, the clinical use of sublingual immunotherapy (SLIT) has dramatically increased. However, 1 of the primary barriers to providing SLIT is lack of a published dosing recommendations. The purpose of this work is to provide a range of effective SLIT dosing based upon a rigorous review of the existing evidence base. An appendix with SLIT dosing recommendations is also included.

Methods: A comprehensive search of the past 25 years of the medical literature using PubMed was performed for specific antigens. Inclusion criteria for articles included: randomized, placebo-controlled studies of SLIT, studies with clinical allergic rhinitis outcomes, and dosing units available to determine the micrograms per month of major allergen administered. The extracted data was used to compile a range of effective SLIT dosing for individual antigens.

Results: Seventy-five articles met the inclusion criteria, providing a range of effective dosing for some allergens. There was commonly a wide range in doses for particular antigens between the individual studies. For some antigens, there was significant overlap in dosage amount between studies showing efficacy and lack of efficacy. Clinical trials meeting inclusion criteria are not available for many allergens.

Conclusion: This study provided a comprehensive review of the published sublingual dosing ranges for specific antigens. The review provided a range of effective sublingual doses for some allergens, whereas for other allergens there was insufficient published data to determine specific doses. Recommendations for SLIT dosing were produced based on the data revealed in the review and expert opinion.
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http://dx.doi.org/10.1002/alr.21561DOI Listing
September 2015

Level of Fatty Acid Binding Protein 5 (FABP5) Is Increased in Sputum of Allergic Asthmatics and Links to Airway Remodeling and Inflammation.

PLoS One 2015 28;10(5):e0127003. Epub 2015 May 28.

Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.

Background: The inflammatory processes in the upper and lower airways in allergic rhinitis and asthma are similar. Induced sputum and nasal lavage fluid provide a non-invasive way to examine proteins involved in airway inflammation in these conditions.

Objectives: We conducted proteomic analyses of sputum and nasal lavage fluid samples to reveal differences in protein abundances and compositions between the asthma and rhinitis patients and to investigate potential underlying mechanisms.

Methods: Induced sputum and nasal lavage fluid samples were collected from 172 subjects with 1) allergic rhinitis, 2) asthma combined with allergic rhinitis, 3) nonallergic rhinitis and 4) healthy controls. Proteome changes in 21 sputum samples were analysed with two-dimensional difference gel electrophoresis (2D-DIGE), and the found differentially regulated proteins identified with mass spectrometry. Immunological validation of identified proteins in the sputum and nasal lavage fluid samples was performed with Western blot and ELISA.

Results: Altogether 31 different proteins were identified in the sputum proteome analysis, most of these were found also in the nasal lavage fluid. Fatty acid binding protein 5 (FABP5) was up-regulated in the sputum of asthmatics. Immunological validation in the whole study population confirmed the higher abundance levels of FABP5 in asthmatic subjects in both the sputum and nasal lavage fluid samples. In addition, the vascular endothelial growth factor (VEGF) level was increased in the nasal lavage fluid of asthmatics and there were positive correlations between FABP5 and VEGF levels (r=0.660, p<0.001) and concentrations of FABP5 and cysteinyl leukotriene (CysLT) (r=0.535, p<0.001) in the nasal lavage fluid.

Conclusions: FABP5 may contribute to the airway remodeling and inflammation in asthma by fine-tuning the levels of CysLTs, which induce VEGF production.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127003PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447257PMC
April 2016

Chronic rhinosinusitis is rare but bothersome in adolescents from a Swedish population-based cohort.

J Allergy Clin Immunol 2015 Aug 1;136(2):512-4.e6. Epub 2015 Apr 1.

Department of Clinical Science, Intervention and Technology, Division of Ear, Nose and Throat Diseases, Karolinska Institutet, Stockholm, Sweden; Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden.

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http://dx.doi.org/10.1016/j.jaci.2015.02.019DOI Listing
August 2015

Local and systemic proteolytic responses in chronic rhinosinusitis with nasal polyposis and asthma.

Int Forum Allergy Rhinol 2015 Apr 3;5(4):294-302. Epub 2015 Feb 3.

Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma coexist frequently and share similar features of inflammation and remodeling. Remodeling has become an important concept in the pathophysiology of asthma and CRSwNP. It happens early in the development of these diseases and is relatively resistant to treatments. The key enzymes responsible for remodeling are matrix metalloproteinases (MMPs). In this study we examined whether asthma and CRSwNP share similar MMP profiles.

Methods: Nasal secretion and serum specimens of controls (19 subjects) and patients with asthma (12), CRSwNP (39), or both (16) were collected between December 2007 and May 2009. Groups were divided into 2 subgroups according to atopy. MMP-7, MMP-9, MMP-13, tissue inhibitors of metalloproteinases (TIMPs), TIMP-1 and TIMP-2, myeloperoxidase (MPO), and human neutrophil elastase (HNE) were measured using enzyme-linked immunosorbent assay (ELISA), and MMP-8 was determined using immunofluorometric assay. High-sensitivity C-reactive protein (hs-CRP) was measured to estimate systemic involvement.

Results: Patients with asthma, CRSwNP, or both exhibited lower MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and MPO in nasal secretions (p < 0.05 in CRSwNP) and higher MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and HNE in serum (p < 0.05 in all groups) compared to controls, whereas no difference in MMP-7, MMP-13, TIMP-1, and TIMP-2 were detected. Atopy increased nasal MMP-9 and MPO expression. hs-CRP was higher in patients with CRSwNP and asthma compared to controls.

Conclusion: Our findings suggest shared pathomechanisms behind asthma and CRSwNP. Contrasting local vs systemic results reflect a different ability of healthy mucosa to react to exogenous stimuli, possibly indicating a protective function of MMP-9 and possibly also MMP-8 in the airways.
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http://dx.doi.org/10.1002/alr.21486DOI Listing
April 2015

Immunology.

Authors:
Elina Toskala

Int Forum Allergy Rhinol 2014 Sep;4 Suppl 2:S21-7

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Temple University, Philadelphia, PA.

Background: Knowledge of our immune system functions is critical for understanding allergic airway disease development as well as for selection of appropriate diagnostic and therapeutic options for patients with respiratory allergies.

Methods: This review explains the current understanding of the basic immunology of the upper airways and the pathophysiology of allergic responses, including the mechanisms behind allergic rhinitis.

Results: The immune system can be divided to 2 main defense systems that function differently-innate immunity and adaptive immunity. Innate immunity includes several defensive mechanisms such as anatomic or physical barriers, physiological barriers, phagocytosis, and inflammation. The adaptive immune response is activated in an antigen-specific way to provide for the elimination of antigen and induce lasting protection. Hypersensitivity reactions occur when an exaggerated adaptive immune response is activated. Allergic rhinitis is an example of a type I, immunoglobulin E, mediated hypersensitivity reaction.

Conclusion: Today we have several immunomodulatory treatment options for patients with allergic airway diseases, such as subcutaneous and sublingual immunotherapy. An understanding of the basics of our immune system and its method of functions is key for using these therapies appropriately.
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http://dx.doi.org/10.1002/alr.21380DOI Listing
September 2014

Update on evidence-based reviews with recommendations in adult chronic rhinosinusitis.

Int Forum Allergy Rhinol 2014 Jul 29;4 Suppl 1:S1-S15. Epub 2014 May 29.

Division of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, UT.

Chronic rhinosinusitis (CRS) has a significant impact not only on individuals who are afflicted but also on society as a whole. An increasing emphasis is being placed on incorporating the best available evidence into the care of patients, in association with an individual clinician's expertise and the patient's values. Recent evidence-based reviews with recommendations (EBRRs) have distilled our knowledge of CRS treatment options and have also pointed out continued gaps in this knowledge. This review synthesizes the findings of 8 EBRRs regarding CRS published in the International Forum of Allergy and Rhinology between 2011 and 2014. The recommendations in this review are based on the best available evidence and are meant to be incorporated into each patient's individual care, along with the practitioner's expertise and the individual patient's values and expectations. It is hoped that the EBRRs, and the process that spawned them, can provide the foundation for future guidelines in the diagnosis and management of CRS.
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http://dx.doi.org/10.1002/alr.21344DOI Listing
July 2014

Sublingual immunotherapy: what we can learn from the European experience.

Curr Opin Otolaryngol Head Neck Surg 2014 Jun;22(3):208-10

Department of Otolaryngology - Head and Neck Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.

Purpose Of Review: To review the recent European studies on sublingual immunotherapy (SLIT). SLIT is currently widely used in Europe and is gaining popularity in the United States.

Recent Findings: Longer treatment with SLIT compared with subcutaneous immunotherapy (SCIT) is needed to reduce the rhinitis symptoms in house dust mite (HDM) allergic children. SLIT appears to be well tolerated and effective for treating rhinitis and asthma in children, adults, and the elderly. Studies on HDM, grass, and ragweed have demonstrated posttreatment efficacy in both monosensitized and polysensitized patients.

Summary: SLIT has been shown to be an effective treatment for airway allergies, and recent studies give support for the use of SLIT as the first choice for allergy treatment compared with medication and SCIT. The use of SLIT may potentially improve the compliance of allergen immunotherapy and may make allergy treatment more accessible and well tolerated.
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http://dx.doi.org/10.1097/MOO.0000000000000042DOI Listing
June 2014

Work-related airway diseases.

Authors:
Elina Toskala

ORL Head Neck Nurs 2013 ;31(4):11-6

Department of Otolaryngology-Head and Neck Surgery Temple University School of Medicine Philadelphia, Pennsylvania, USA.

Work-related airway symptoms are very common. Occupational asthma may be present in up to 11 million American workers, and many more may also have occupational rhinitis. These illnesses can be related to both allergic and non-allergic mechanisms, and can be difficult to characterize and diagnose. A multidisciplinary approach to diagnosis and management is important to optimize recognition and treatment of these complex patients. The ORL nurse plays a key role in the workup and management of patients with work-related airway diseases.
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April 2014

Genetic variation in genes encoding airway epithelial potassium channels is associated with chronic rhinosinusitis in a pediatric population.

PLoS One 2014 3;9(3):e89329. Epub 2014 Mar 3.

Department of Otolaryngology, Temple University, Philadelphia, Pennsylvania, United States of America.

Background: Apical potassium channels regulate ion transport in airway epithelial cells and influence air surface liquid (ASL) hydration and mucociliary clearance (MCC). We sought to identify whether genetic variation within genes encoding airway potassium channels is associated with chronic rhinosinusitis (CRS).

Methods: Single nucleotide polymorphism (SNP) genotypes for selected potassium channels were derived from data generated on the Illumnia HumanHap550 BeadChip or Illumina Human610-Quad BeadChip for 828 unrelated individuals diagnosed with CRS and 5,083 unrelated healthy controls from the Children's Hospital of Philadelphia (CHOP). Statistical analysis was performed with set-based tests using PLINK, and corrected for multiple testing.

Results: Set-based case control analysis revealed the gene KCNMA1 was associated with CRS in our Caucasian subset of the cohort (598 CRS cases and 3,489 controls; p = 0.022, based on 10,000 permutations). In addition there was borderline evidence that the gene KCNQ5 (p = 0.0704) was associated with the trait in our African American subset of the cohort (230 CRS cases and 1,594 controls). In addition to the top significant SNPs rs2917454 and rs6907229, imputation analysis uncovered additional genetic variants in KCNMA1 and in KCNQ5 that were associated with CRS.

Conclusions: We have implicated two airway epithelial potassium channels as novel susceptibility loci in contributing to the pathogenesis of CRS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089329PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940609PMC
January 2015

Nasal nitric oxide is dependent on sinus obstruction in allergic rhinitis.

Laryngoscope 2014 Jun 10;124(6):E213-8. Epub 2014 Feb 10.

Control of Hypersensitivity Diseases Team, Finnish Institute of Occupational Health, Helsinki, Finland.

Objectives/hypothesis: The aim of this study was to evaluate the associations between nasal nitric oxide and nasal symptoms, sinus opacification, and markers of allergic inflammation in allergic and in nonallergic rhinitis while taking into account the effect of sinus obstruction.

Study Design: We studied 175 young adult subjects divided into three groups: 1) allergic rhinitis, 2) nonallergic rhinitis, and 3) controls.

Methods: We measured nasal nitric oxide using the breath-holding method and exhaled nitric oxide and scored semiquantitatively nasal computed tomography scans for opacification and obstruction. We also assessed the visual analogue scores of nasal symptoms, eosinophil count, and interleukin-13 mRNA levels in nasal biopsies.

Results: The level of nasal nitric oxide correlated with exhaled nitric oxide (r = 0.377, P < .001). In allergic rhinitis, nasal nitric oxide was elevated when compared to the controls, and an inverse correlation existed between the nasal nitric oxide level and sinus ostial obstruction (r = -0.272, P = .013). In nonallergic rhinitis, the level of nasal nitric oxide was similar to that of the controls. In allergic rhinitis, nasal nitric oxide correlated positively with the opacification score (r = 0.250, P = .033) and the nasal eosinophil count (r = 0.293, P = .030) of patients without a marked sinus ostial obstruction.

Conclusions: Sinus ostial obstruction lowers the level of nasal nitric oxide and reduces its value as an indicator of allergic mucosal inflammation. A high nasal nitric oxide level may be a useful marker of eosinophilic inflammation in the nasal cavity and indicate the absence of marked sinus ostial obstruction.

Level Of Evidence: 3b.
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http://dx.doi.org/10.1002/lary.24590DOI Listing
June 2014

Why otolaryngologists and asthma are a good match: the allergic rhinitis-asthma connection.

Otolaryngol Clin North Am 2014 Feb;47(1):1-12

Department of Otolaryngology, Temple University Health System, 3509 North Broad Street, Philadelphia, PA 19140-4105, USA.

Consideration of the unified airway model when managing patients with rhinitis and or asthma allows a more comprehensive care plan and therefore improved patient outcomes. Asthma is linked to rhinitis both epidemiologically and biologically, and this association is even stronger in individuals with atopy. Rhinitis is not only associated with but is a risk factor for the development of asthma. Management of rhinitis improves asthma control. Early and aggressive treatment of allergic rhinitis may prevent the development of asthma. In patients with allergic rhinitis that is not sufficiently controlled by allergy medication, allergen-directed immunotherapy should be considered.
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http://dx.doi.org/10.1016/j.otc.2013.08.016DOI Listing
February 2014