F Estelle R Simons

University of Manitoba, Winnipeg, Manitoba, Canada

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Publications (406)2782.27 Total impact

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    ABSTRACT: In the past few years there have been significant advances which have changed the face of chronic urticaria. In this review, we aim to update physicians about clinically relevant advances in the classification, diagnosis and management of chronic urticaria that have occurred in recent years. These include clarification of the terminology used to describe and classify urticaria. We also detail the development and validation of instruments to assess urticaria and understand the impairment on quality-of-life and the morbidity caused by this disease. Additionally, the approach to management of chronic urticaria now focuses on evidence-based use of non-impairing, non-sedating H1-antihistamines given initially in standard doses and if this is not effective, in up to 4-fold doses. For urticaria refractory to H1-antihistamines, omalizumab treatment has emerged as an effective, safe option.
    Allergy Asthma and Clinical Immunology 12/2015; 11(1):7. DOI:10.1186/s13223-015-0072-2 · 2.03 Impact Factor
  • Gordon L Sussman · Jacques Hebert · F Estelle R Simons ·

    Canadian Medical Association Journal 11/2015; DOI:10.1503/cmaj.150154 · 5.96 Impact Factor
  • Ulugbek B Nurmatov · Edmund Rhatigan · F Estelle R Simons · Aziz Sheikh ·
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    ABSTRACT: Primary mast cell activation syndromes (MCAS) are a group of disorders presenting with symptoms of mast cell mediator release. To assess the effectiveness and safety of orally-administered H1 -antihistamines in the treatment of primary MCAS compared with placebo and other pharmacologic treatments. We systematically searched five databases, three trial repositories and contacted an international panel of experts to identify published and unpublished trials, enrolling a total of 71 patients (63 adults). 36 potentially relevant studies were identified. Of these, five crossover trials met the eligibility criteria. Five of these studies were judged to be at moderate or high risk of bias. Two studies compared an H1 -antihistamine with placebo, two compared two different H1 - antihistamines, and one study compared H1 - and H2 -antihistamines with oral cromolyn sodium. Four of the five RCTs were historic (reported from 1983-93), small (enrolling 8-15 patients), and used agents and/or dosing regimens that are now uncommonly used in clinical practice (i.e. azelastine, chlorpheniramine, hydroxyzine and ketotifen). The fifth trial, which enrolled 33 adults with cutaneous and systemic mastocytosis found four weeks of treatment with the second-generation H1 -antihistamine rupatadine, compared with placebo, resulted in significant improvements in quality of life, symptom control (itching, wheals and flares, flushing, tachycardia, and headache, but not gastrointestinal symptoms), and reduction of itching and whealing after standardized skin provocation to elicit Darier's sign. There is an urgent need for large, well-designed, double-blind, placebo-controlled randomized trials investigating the effectiveness, cost-effectiveness and safety of second-generation H1 -antihistamines in treatment of primary MCAS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Allergy 06/2015; 70(9). DOI:10.1111/all.12672 · 6.03 Impact Factor
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    ABSTRACT: Prompt injection of epinephrine (adrenaline) from epinephrine auto-injectors (EAIs) is the primary treatment for anaphylaxis in out-of-hospital settings. Storage of EAIs at room temperature (25 °C) is advised; however, storage at excessively high temperatures sometimes occurs. To our knowledge, there are no previous publications on the doses of epinephrine ejected from EAIs after storage at such temperatures. We examined the epinephrine doses delivered from activated EAIs stored constantly or cyclically at 70 °C. Twenty-five in-date EAIs were stored constantly or cyclically at 70 °C (excessive heat) or 25 °C (controls) for 5 d or 10 d. EAIs were activated and the epinephrine doses in the ejected solutions were measured using HPLC-UV. The enantiomeric purity of epinephrine was also measured by HPLC-UV. Control EAIs ejected a volume of 0.300 ± 0.006 mL containing 103.7 ± 3.3% of labeled dose (LD). After 5 d or 10 d of constant storage at 70 °C and activation at 70 °C, EAIs ejected a volume of 0.367 ± 0.008 mL containing 96.8 ± 3.8% LD and 0.373 ± 0.007 mL containing 77.7 ± 3.3% LD, respectively. After 5 d of cyclic storage at 70 °C and cooling to 25 °C before activation, EAIs ejected a volume of 0.311 ± 0.008 mL containing 87.2 ± 1.9% LD. Under the experimental conditions of this study, the resultant chromatographic peaks of epinephrine solutions from all EAIs represented only the pure l-enantiomer of epinephrine. EAIs should be stored under recommended conditions of the manufacturer. EAIs stored at excessively high temperatures cannot be used to treat humans while still hot, and when cooled, cannot be relied on to deliver the labeled epinephrine dose in anaphylaxis.
    Drug Development and Industrial Pharmacy 05/2015; DOI:10.3109/03639045.2015.1035283 · 2.10 Impact Factor
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    ABSTRACT: For the first-aid treatment of anaphylaxis, epinephrine (Epi) 0.3 mg intramuscular (IM) injection in the thigh is the drug of choice. Epi auto-injectors are widely recommended for anaphylaxis treatment in community settings but not necessarily carried or used as prescribed when anaphylaxis occurs. We therefore developed rapidly disintegrating sublingual tablets (RDSTs) as an alternative noninvasive dosage form. Our objective in this study was to evaluate the effect of reducing Epi particle size on its in vitro and ex vivo diffusion, with the goal of enhancing Epi sublingual absorption from Epi RDSTs. Epi particle size was reduced by top-bottom technique using a microfluidizer for one pass at 30,000 Psi. The micronized Epi crystals (Epi-MC) were characterized using Zetasizer, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Epi RDSTs were formulated and manufactured using our previously developed method. In vitro and ex vivo diffusion of Epi 10, 20, and 40 mg RDSTs and Epi-MC 10 and 20 mg RDSTs (n = 4) were evaluated using Franz cells. Epi 10 mg solution was used as a control. Mean (±standard deviation (SD)) Epi particle size was successfully reduced from 131.8 ± 10.5 to 2.5 ± 0.4 μm. Cumulative Epi diffused and influx from 40 mg Epi RDSTs and 20 mg Epi-MC RDSTs were not significantly different from each other in vitro and ex vivo (p > 0.05). Also, Epi permeability from 20 mg Epi-MC RDSTs was significantly higher than from the rest (p < 0.05). Epi-MC RDSTs improved Epi diffusion twofold and might have the potential to reduce the Epi dose needed in RDSTs by 50%.
    AAPS PharmSciTech 03/2015; 16(5). DOI:10.1208/s12249-015-0306-0 · 1.64 Impact Factor
  • Phil Lieberman · F Estelle R Simons ·
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    ABSTRACT: Cardiovascular disease (CVD) increases the risk of severe or fatal anaphylaxis. Some medications used to treat CVD can exacerbate anaphylaxis. To review anaphylaxis and the heart, the potential impact of medications for CVD on anaphylaxis and anaphylaxis treatment, and the cardiovascular effects of epinephrine; to examine the therapeutic dilemmas arising from these issues and propose a way forward. PubMed searches were performed for the years 1990-2014 inclusive, using terms such as angiotensin-converting enzyme (ACE) inhibitors, adrenaline, allergic myocardial infarction, anaphylaxis, angiotensin-receptor blockers (ARBs), beta-adrenergic blockers, epinephrine, and Kounis syndrome. Cardiac mast cells are key constituents of atherosclerotic plaques. Mast cell mediators play an important role in acute coronary syndrome (ACS). Patients with CVD have an increased risk of developing severe or fatal anaphylaxis. Medications used in CVD treatment, including beta-adrenergic blockers and ACE inhibitors, potentially exacerbate anaphylaxis, and beta-blockers can make it more difficult to treat. Epinephrine increases myocardial contractility, decreases the duration of systole relative to diastole, and enhances coronary blood flow. Its transient adverse effects include pallor, tremor, anxiety, and palpitations. Its serious adverse effects, including ventricular arrhythmias and hypertension are significantly more likely after i.v. injection than after i.m. injection. Epinephrine is life-saving in anaphylaxis; second-line medications including antihistamines and glucocorticoids are not. In patients with CVD (especially those with ACS), the decision to administer epinephrine for anaphylaxis can be difficult, and its benefits and harms need to be carefully considered. There is no absolute contraindication to epinephrine injection in anaphylaxis. Concerns about potential adverse effects need to be weighed against concerns about possible death from untreated anaphylaxis. The evidence for optimal acute and long-term management of CVD patients with anaphylaxis or increased risk of anaphylaxis needs strengthening. The development of multispecialty management guidelines should be considered. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 02/2015; 45(8). DOI:10.1111/cea.12520 · 4.77 Impact Factor

  • Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 02/2015; 114(4). DOI:10.1016/j.anai.2015.01.015 · 2.60 Impact Factor

  • 01/2015; 3(2). DOI:10.1016/j.jaip.2014.11.015
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    ABSTRACT: In a review of rupatadine published in 2008, the primary focus was on its role as an antihistamine, with a thorough evaluation of its pharmacology and interaction with histamine H1 -receptors. At the time, however, evidence was already emerging of a broader mechanism of action for rupatadine involving other mediators implicated in the inflammatory cascade. Over the past few years, the role of platelet-activating factor (PAF) as a potent mediator involved in the hypersensitivity-type allergic reaction has gained greater recognition. Rupatadine has dual affinity for histamine H1 -receptors and PAF receptors. In view of the Allergic Rhinitis and its Impact on Asthma group's call for oral antihistamines to exhibit additive anti-allergic/anti-inflammatory properties, further exploration of rupatadine's anti-PAF effects was a logical step forward. New studies have demonstrated that rupatadine inhibits PAF effects in nasal airways and produces a greater reduction in nasal symptoms than levocetirizine. A meta-analysis involving more than 2500 patients has consolidated the clinical evidence for rupatadine in allergic rhinoconjunctivitis in adults and children (level of evidence Ia, recommendation A). Other recent advances include observational studies of rupatadine in everyday clinical practice situations and approval of a new formulation (1 mg/ml oral solution) for use in children. In this reappraisal, we revisit some key properties and pivotal clinical studies of rupatadine and examine new clinical data in more detail including studies that measured health-related quality of life and studies that investigated the efficacy and safety of rupatadine in other indications such as acquired cold urticaria, mosquito bite allergy and mastocytosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Allergy 01/2015; 70 Suppl 100(s100):1-24. DOI:10.1111/all.12531 · 6.03 Impact Factor

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    Przegla̧d dermatologiczny 01/2015; 2:155-179. DOI:10.5114/dr.2015.51433

  • Journal of Allergy and Clinical Immunology 12/2014; 135(3). DOI:10.1016/j.jaci.2014.10.049 · 11.48 Impact Factor
  • Eric S Edwards · Evan T Edwards · F Estelle R Simons · Robert North ·
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    ABSTRACT: Introduction: The systematic application of human factors engineering (HFE) principles to the development of drug-device combination products, including epinephrine auto-injectors (EAIs), has the potential to improve the effectiveness and safety of drug administration. Areas covered: A PubMed search was performed to assess the role of HFE in the development of drug-device combination products. The following keywords were used in different combinations: 'human factors engineering,' 'human factors,' 'medical products,' 'epinephrine/adrenaline auto-injector,' 'healthcare' and 'patient safety.' This review provides a summary of HFE principles and their application to the development of drug-device combination products as advised by the US FDA. It also describes the HFE process that was applied to the development of Auvi-Q, a novel EAI, highlighting specific steps that occurred during the product-development program. Expert opinion: For drug-device combination products, device labeling and usability are critical and have the potential to impact clinical outcomes. Application of HFE principles to the development of drug-delivery devices has the potential to improve product quality and reliability, reduce risk and improve patient safety when applied early in the development process. Additional clinical and real-world studies will confirm whether the application of HFE has helped to develop an EAI that better meets the needs of patients at risk of anaphylaxis.
    Expert Opinion on Drug Delivery 12/2014; 12(5):1-12. DOI:10.1517/17425247.2015.987660 · 4.84 Impact Factor
  • F Estelle R Simons · Hugh A Sampson ·
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    ABSTRACT: In this rostrum we aim to increase awareness of anaphylaxis in infancy in order to improve clinical diagnosis, management, and prevention of recurrences. Anaphylaxis is increasingly reported in this age group. Foods are the most common triggers. Presentation typically involves the skin (generalized urticaria), the respiratory tract (cough, wheeze, stridor, and dyspnea), and/or the gastrointestinal tract (persistent vomiting). Tryptase levels are seldom increased because of infant anaphylaxis, although baseline tryptase levels can be increased in the first few months of life, reflecting mast cell burden in the developing immune system. The differential diagnosis of infant anaphylaxis includes consideration of age-unique entities, such as food protein-induced enterocolitis syndrome with acute presentation. Epinephrine (adrenaline) treatment is underused in health care and community settings. No epinephrine autoinjectors contain an optimal dose for infants weighing 10 kg or less. After treatment of an anaphylactic episode, follow-up with a physician, preferably an allergy/immunology specialist, is important for confirmation of anaphylaxis triggers and prevention of recurrences through avoidance of confirmed specific triggers. Natural desensitization to milk and egg can occur. Future research should include validation of the clinical criteria for anaphylaxis diagnosis in infants, prospective longitudinal monitoring of baseline serum tryptase levels in healthy and atopic infants during the first year of life, studies of infant comorbidities and cofactors that increase the risk of severe anaphylaxis, development of autoinjectors containing a 0.1-mg epinephrine dose suitable for infants, and inclusion of infants in prospective studies of immune modulation to prevent anaphylaxis recurrences. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Journal of Allergy and Clinical Immunology 10/2014; 135(5). DOI:10.1016/j.jaci.2014.09.014 · 11.48 Impact Factor
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    ABSTRACT: Objectives For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model.Methods The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively.Key findingsEpimean(standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P < 0.05) than after placebo RDSTs administration (reflecting endogenous adrenaline levels).Conclusion Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings.
    10/2014; 67(1). DOI:10.1111/jphp.12312
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    ABSTRACT: ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public.
    World Allergy Organization Journal 05/2014; 7(1):9. DOI:10.1186/1939-4551-7-9
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    ABSTRACT: This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).
    Allergy 04/2014; 69(7). DOI:10.1111/all.12313 · 6.03 Impact Factor
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    Ulugbek B Nurmatov · Edmund Rhatigan · F Estelle R Simons · Aziz Sheikh ·
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    ABSTRACT: Anaphylaxis is a serious allergic or hypersensitivity reaction, which is rapid in onset and sometimes can prove fatal. Although H2-antihistamines are often administered for emergency treatment in anaphylaxis, there is uncertainty about their effectiveness in this disease. To assess the benefits and harms of H2-antihistamines in the treatment of anaphylaxis. A systematic review was performed of randomized controlled trials and quasi-randomized controlled trials comparing H2-antihistamines with placebo or no intervention in patients with anaphylaxis. The authors failed to identify any eligible studies for inclusion in this systematic review. When H2-antihistamines are recommended for anaphylaxis treatment, the status of the evidence base supporting their use should be described. Well-designed randomized controlled trials investigating the role of H2-antihistamines in anaphylaxis treatment are urgently needed.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 02/2014; 112(2):126-31. DOI:10.1016/j.anai.2013.11.010 · 2.60 Impact Factor

  • Journal of Allergy and Clinical Immunology 02/2014; 133(2):AB166. DOI:10.1016/j.jaci.2013.12.599 · 11.48 Impact Factor
  • Mutasem M Rawas-Qalaji · Ousama Rachid · F Estelle R Simons · Keith J Simons ·

    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 12/2013; 111(6):568-570. DOI:10.1016/j.anai.2013.09.005 · 2.60 Impact Factor

Publication Stats

17k Citations
2,782.27 Total Impact Points


  • 1978-2015
    • University of Manitoba
      • • Department of Pediatrics and Child Health
      • • Department of Immunology
      • • Faculty of Medicine
      • • Faculty of Pharmacy
      Winnipeg, Manitoba, Canada
  • 2010
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1989-2010
    • Health Sciences Centre Winnipeg
      Winnipeg, Manitoba, Canada
  • 1978-2008
    • Government of Manitoba, Canada
      Winnipeg, Manitoba, Canada
  • 2007
    • The University of Edinburgh
      • Centre for Population Health Sciences
      Edinburgh, Scotland, United Kingdom
  • 2006
    • European Academy of Allergy and Clinical Immunology
      Zürich, Zurich, Switzerland
    • American Academy of Allergy Asthma & Immunology
      Американ Форк, Utah, United States
  • 1979-2005
    • The University of Winnipeg
      Winnipeg, Manitoba, Canada
  • 2002
    • University of California, San Diego
      San Diego, California, United States
  • 1984-1999
    • Canadian Society of Allergy and Clinical Immunology
      Winnipeg, Manitoba, Canada
  • 1975-1977
    • University of Washington Seattle
      • • Department of Pharmacy
      • • Department of Medicine
      Seattle, Washington, United States