Publications by authors named "Glenis K Scadding"

47 Publications

Innate and adaptive immunity: ILC2 and Th2 cells in upper and lower airway allergic diseases.

J Allergy Clin Immunol Pract 2021 Feb 19. Epub 2021 Feb 19.

Royal Brompton Hospital, London, UK.

Advances in our understanding of the immune system, with the recent discovery of a parallel set of innate T lymphocytes, the ILCs, have led to a reassessment of the pathogenesis of allergic and eosinophilic airway disorders, including allergic rhinitis, asthma and chronic rhinosinusitis with nasal polyps. We review current understanding of both elements of type-2 inflammatory responses and their relative influence in these common conditions and consider possible impacts of this on treatment selection.
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http://dx.doi.org/10.1016/j.jaip.2021.02.013DOI Listing
February 2021

Evaluating the real-life effect of MP-AzeFlu on asthma outcomes in patients with allergic rhinitis and asthma in UK primary care.

World Allergy Organ J 2020 Dec 19;13(12):100490. Epub 2020 Dec 19.

Observational and Pragmatic Research Institute, Singapore.

Background: MP-AzeFlu (Dymista®; spray of azelastine/fluticasone propionate) is the most effective allergic rhinitis (AR) treatment available. Its effect on asthma outcomes in patients with AR and asthma is unknown.

Methods: This pre-post historical cohort study, using the Optimum Patient Care Research Database, included patients aged ≥12 years, from UK general practice with active asthma (defined as a recorded diagnosis, with ≥1 prescription for reliever or controller inhaler) in the year before or at the initiation date. The primary study outcome was change in number of acute respiratory events (i.e. exacerbation or antibiotic course for a respiratory event) between baseline and outcome years. The effect size of MP-AzeFlu was quantified as the difference in % of patients that improved and worsened.

Results: Of the 1,188 patients with AR and asthma included, many had a record of irreversible obstruction (67%), and uncontrolled asthma (70.4%), despite high mean daily doses of reliever/controller therapy and acute oral corticosteroid use, in the year pre-MP-AzeFlu initiation. MP-AzeFlu initiation was associated with fewer acute respiratory events (effect size (e) = 5.8%, p = 0.0129) and a reduction in daily use of short-acting β-agonists, with fewer patients requiring >2 SABA puffs/week (e = 7.7% p < 0.0001). More patients had well-controlled asthma 1-year post-MP-AzeFlu initiation (e = 4.1%; p = 0.0037), despite a reduction in inhaled corticosteroids (e = 4.8%; p = 0.0078).

Conclusions: This study provides the first direct evidence of the beneficial effect of MP-AzeFlu on asthma outcomes in co-morbid patients in primary care in the United Kingdom.

Trial Registration: EUPAS30940. Registered August 13, 2019.
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http://dx.doi.org/10.1016/j.waojou.2020.100490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753940PMC
December 2020

MP-AzeFlu Improves the Quality-of-Life of Patients with Allergic Rhinitis.

J Asthma Allergy 2020 2;13:633-645. Epub 2020 Dec 2.

Rhinology Unit & Smell Clinic, ENT Department, Hospital Clinic Barcelona IDIBAPS University of Barcelona, CIBERES, Barcelona, Catalonia, Spain.

Purpose: Patients with poorly controlled allergic rhinitis (AR) experience nasal symptoms, sleep disturbances, activity impairment, and decreased quality-of-life (QoL). MP-AzeFlu is safe and effective for moderate-to-severe seasonal and perennial AR, but its impact on QoL requires investigation in the real-world, especially among phenotypes of immunoglobulin (Ig)E-mediated AR. This subanalysis of an observational study evaluated response to MP-AzeFlu via assessment of sleep quality and trouble with daily activities.

Patients And Methods: This multicenter, prospective, non-interventional, real-life study included a convenience sample of patients with a history of moderate-to-severe AR presenting with acute AR symptoms (visual analog scale [VAS] ≥50 mm). Over approximately 14 days of treatment with MP-AzeFlu (137 µg azelastine HCL and 50 µg fluticasone propionate administered via single 0.137-mL spray in each nostril twice daily), changes in sleep quality and trouble with daily work, school, social, and outdoor activities were evaluated using a VAS for the entire study population and for four subgroups based on IgE response phenotype. VAS scores ranged from "not at all troubled" (0 mm) to "extremely troubled" (100 mm).

Results: Following MP-AzeFlu treatment, mean VAS scores for sleep quality impairment and work or school impairment decreased from 55.2 mm at baseline to 22.1 mm and 57.6 mm at baseline to 23.0 mm, respectively, after ~14 days. Similar results were observed for mean VAS scores for impairment of social activity (55.1 mm to 22.4 mm) and impairment of outdoor activity (64.4 mm to 25.0 mm). For all VAS scores, results were similar across populations, regardless of phenotype of IgE-mediated disease, comorbidity, age, and sex.

Conclusion: MP-AzeFlu relieves symptoms and improves patient-reported QoL, illustrated by better sleep quality and less impairment of work, school, social, and outdoor activities after 14 days. The QoL benefits of MP-AzeFlu were consistent regardless of the phenotype of IgE-mediated disease.

Registration: Clinical Trial Registration (CTR) Number: EUPAS23075. Trial Register Date: March 12, 2018. First patient visit; Last patient visit: February 2018; April 2019.
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http://dx.doi.org/10.2147/JAA.S277734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719305PMC
December 2020

Allergic rhinitis.

Nat Rev Dis Primers 2020 12 3;6(1):95. Epub 2020 Dec 3.

Skin and Allergy Hospital, Karolinska Institutet, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Allergic rhinitis (AR) is caused by immunoglobulin E (IgE)-mediated reactions to inhaled allergens and is one of the most common chronic conditions globally. AR often co-occurs with asthma and conjunctivitis and is a global health problem causing major burden and disability worldwide. Risk factors include inhalant and occupational allergens, as well as genetic factors. AR impairs quality of life, affects social life, school and work, and is associated with substantial economic costs. The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative classified AR into intermittent or persistent and mild or moderate/severe. The diagnosis is based on the clinical history and, if needed in patients with uncontrolled rhinitis despite medications or with long-lasting symptoms, on skin tests or the presence of serum-specific IgE antibodies to allergens. The most frequently used pharmacological treatments include oral, intranasal or ocular H-antihistamines, intranasal corticosteroids or a fixed combination of intranasal H-antihistamines and corticosteroids. Allergen immunotherapy prescribed by a specialist using high-quality extracts in stratified patients is effective in patients with persistent symptoms. Real-world data obtained by mobile technology offer new insights into AR phenotypes and management. The outlook for AR includes a better understanding of novel multimorbid phenotypes, health technology assessment and patient-centred shared decision-making.
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http://dx.doi.org/10.1038/s41572-020-00227-0DOI Listing
December 2020

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Authors:
Jean Bousquet Josep M Anto Claus Bachert Tari Haahtela Torsten Zuberbier Wienczyslawa Czarlewski Anna Bedbrook Sinthia Bosnic-Anticevich G Walter Canonica Victoria Cardona Elisio Costa Alvaro A Cruz Marina Erhola Wytske J Fokkens Joao A Fonseca Maddalena Illario Juan-Carlos Ivancevich Marek Jutel Ludger Klimek Piotr Kuna Violeta Kvedariene Ltt Le Désirée E Larenas-Linnemann Daniel Laune Olga M Lourenço Erik Melén Joaquim Mullol Marek Niedoszytko Mikaëla Odemyr Yoshitaka Okamoto Nikos G Papadopoulos Vincenzo Patella Oliver Pfaar Nhân Pham-Thi Christine Rolland Boleslaw Samolinski Aziz Sheikh Mikhail Sofiev Charlotte Suppli Ulrik Ana Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Sian Williams Arzu Yorgancioglu Ioana Agache Cezmi A Akdis Rute Almeida Ignacio J Ansotegui Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagaña Eric D Bateman Annabelle Bédard Martin Bedolla-Barajas Sven Becker Kazi S Bennoor Samuel Benveniste Karl C Bergmann Michael Bewick Slawomir Bialek Nils E Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Matteo Bonini Philippe Bonniaud Isabelle Bosse Jacques Bouchard Louis-Philippe Boulet Rodolphe Bourret Koen Boussery Fluvio Braido Vitalis Briedis Andrew Briggs Christopher E Brightling Jan Brozek Guy Brusselle Luisa Brussino Roland Buhl Roland Buonaiuto Moises A Calderon Paulo Camargos Thierry Camuzat Luis Caraballo Ana-Maria Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Niels H Chavannes Ekaterine Chkhartishvili Derek K Chu Cemal Cingi Jaime Correia de Sousa David J Costa Anne-Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejan Dokic Yves Dauvilliers Giulia De Feo Govert De Vries Philippe Devillier Stefania Di Capua Gerard Dray Ruta Dubakiene Stephen R Durham Mark Dykewicz Motohiro Ebisawa Mina Gaga Yehia El-Gamal Enrico Heffler Regina Emuzyte John Farrell Jean-Luc Fauquert Alessandro Fiocchi Antje Fink-Wagner Jean-François Fontaine José M Fuentes Perez Bilun Gemicioğlu Amiran Gamkrelidze Judith Garcia-Aymerich Philippe Gevaert René Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam Yunuen R Huerta Villalobos Marc Humbert Guido Iaccarino Despo Ierodiakonou Tomohisa Iinuma Ewa Jassem Guy Joos Ki-Suck Jung Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Musa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Rostislav Kouznetsov Marek L Kowalski Vicky Kritikos Inger Kull Stefania La Grutta Lisa Leonardini Henrik Ljungberg Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Catarina Lopes-Pereira Claudia C Loureiro Renaud Louis Alpana Mair Bassam Mahboub Michaël Makris Joao Malva Patrick Manning Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Pedro Carreiro-Martins Mika Makela Eve Mathieu-Dupas Marcus Maurer Esteban De Manuel Keenoy Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Yann Micheli Neven Miculinic Florin Mihaltan Branislava Milenkovic Dimitirios I Mitsias Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralph Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leyla Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Björn Nordlund Ettore Novellino Dieudonné Nyembue Robyn O'Hehir Ken Ohta Kimi Okubo Gabrielle L Onorato Valentina Orlando Solange Ouedraogo Julia Palamarchuk Isabella Pali-Schöll Peter Panzner Hae-Sim Park Gianni Passalacqua Jean-Louis Pépin Ema Paulino Ruby Pawankar Jim Phillips Robert Picard Hilary Pinnock Davor Plavec Todor A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Fotis Psarros Benoit Pugin Francesca Puggioni Pablo Quinones-Delgado Filip Raciborski Rojin Rajabian-Söderlund Frederico S Regateiro Sietze Reitsma Daniela Rivero-Yeverino Graham Roberts Nicolas Roche Erendira Rodriguez-Zagal Christine Rolland Regina E Roller-Wirnsberger Nelson Rosario Antonino Romano Menachem Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Joaquin Sastre Glenis K Scadding Sophie Scheire Peter Schmid-Grendelmeier Holger J Schünemann Faradiba Sarquis Serpa Mohamed Shamji Juan-Carlos Sisul Mikhail Sofiev Dirceu Solé David Somekh Talant Sooronbaev Milan Sova François Spertini Otto Spranger Cristiana Stellato Rafael Stelmach Michel Thibaudon Teresa To Mondher Toumi Omar Usmani Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Marilyn Urrutia Pereira Rianne van der Kleij Michiel Van Eerd Olivier Vandenplas Tuula Vasankari Antonio Vaz Carneiro Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Yun Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Osman M Yusuf Heather J Zar Stéphane Zeng Mario E Zernotti Luo Zhang Nan Shan Zhong Mihaela Zidarn

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

Allergic respiratory disease care in the COVID-19 era: A EUFOREA statement.

World Allergy Organ J 2020 May 16;13(5):100124. Epub 2020 May 16.

Charite, Berlin, Germany.

Spring and Summer 2020 are unique in that the challenges of care for those suffering from pollen allergy coincide with the COVID-19 pandemic. Several considerations are important to allow optimal care of allergic rhinitis (AR) and asthma and hence prevention of coronavirus spread through sneezing, rhinorrhoea, and coughing. This compact overview of recommendations by the EUFOREA expert teams on allergic airway diseases and allergen-specific immunotherapy (AIT) is based on investigation of the current COVID-19 literature in association with the key words above and shared clinical experience of the experts involved. It deals with similarities and differences between AR and coronavirus infection, specific recommendations for allergic disease care in the COVID-19 era, including guidance on AIT.
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http://dx.doi.org/10.1016/j.waojou.2020.100124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229977PMC
May 2020

Higher efficacy of rupatadine 20 mg and 10 mg versus placebo in patients with perennial allergic rhinitis: a pooled responder analysis.

Allergy Asthma Clin Immunol 2020 23;16:29. Epub 2020 Apr 23.

2CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Catalonia Spain.

Background: The clinical efficacy of rupatadine in terms of responders has not been previously explored in perennial allergic rhinitis (PAR).

Methods: This pooled analysis included data from 6 randomised, double-blind, placebo-controlled trials conducted in PAR patients treated with rupatadine 10 mg or 20 mg, or placebo. Participants were aged ≥ 18 years, with diagnosis of PAR and a Total 4 Nasal Symptom Score (T4NSS) ≥ 5. We evaluated the T4NSS and Total 5 Symptom Score (T5SS) for 28 days of treatment, the responder proportion (50% and 75% response), and the time to response.

Results: Efficacy data from 1486 patients were analysed: 585 received placebo, 682 rupatadine 10 mg, and 219 rupatadine 20 mg. Compared with placebo, rupatadine promoted greater symptom improvements and higher responder proportions (50% and 75% response) for T4NSS and T5SS over 28 days. Symptom improvements and responder proportions were higher in the rupatadine 20 mg group vs the 10 mg group. The time to response was shorter in the rupatadine 20 mg group vs the 10 mg group for T4NSS (16 and 9 days for the 50% and 75% responses, respectively) and for T5SS (13 and 8 days for the 50% and 75% responses, respectively).

Conclusions: Rupatadine was efficacious in reducing allergic rhinitis symptoms, showing high responder proportions. The faster and stronger effect of rupatadine 20 mg may suggest its use in patients with severe PAR or not responding to the standard dose.
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http://dx.doi.org/10.1186/s13223-020-00425-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181536PMC
April 2020

Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence.

Authors:
Jean Bousquet Holger J Schünemann Akdis Togias Claus Bachert Martina Erhola Peter W Hellings Ludger Klimek Oliver Pfaar Dana Wallace Ignacio Ansotegui Ioana Agache Anna Bedbrook Karl-Christian Bergmann Mike Bewick Philippe Bonniaud Sinthia Bosnic-Anticevich Isabelle Bossé Jacques Bouchard Louis-Philippe Boulet Jan Brozek Guy Brusselle Moises A Calderon Walter G Canonica Luis Caraballo Vicky Cardona Thomas Casale Lorenzo Cecchi Derek K Chu Elisio M Costa Alvaro A Cruz Wienczyslawa Czarlewski Gennaro D'Amato Philippe Devillier Mark Dykewicz Motohiro Ebisawa Jean-Louis Fauquert Wytske J Fokkens Joao A Fonseca Jean-François Fontaine Bilun Gemicioglu Roy Gerth van Wijk Tari Haahtela Susanne Halken Despo Ierodiakonou Tomohisa Iinuma Juan-Carlos Ivancevich Marek Jutel Igor Kaidashev Musa Khaitov Omer Kalayci Jorg Kleine Tebbe Marek L Kowalski Piotr Kuna Violeta Kvedariene Stefania La Grutta Désirée Larenas-Linnemann Susanne Lau Daniel Laune Lan Le Philipp Lieberman Karin C Lodrup Carlsen Olga Lourenço Gert Marien Pedro Carreiro-Martins Erik Melén Enrica Menditto Hugo Neffen Gregoire Mercier Ralph Mosgues Joaquim Mullol Antonella Muraro Leyla Namazova Ettore Novellino Robyn O'Hehir Yoshitaka Okamoto Ken Ohta Hae Sim Park Petr Panzner Giovanni Passalacqua Nhan Pham-Thi David Price Graham Roberts Nicolas Roche Christine Rolland Nelson Rosario Dermot Ryan Boleslaw Samolinski Mario Sanchez-Borges Glenis K Scadding Mohamed H Shamji Aziz Sheikh Ana-Maria Todo Bom Sanna Toppila-Salmi Ioana Tsiligianni Marylin Valentin-Rostan Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Susan Waserman Arzu Yorgancioglu Torsten Zuberbier

J Allergy Clin Immunol 2020 01 15;145(1):70-80.e3. Epub 2019 Oct 15.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Uniersität zu Berlin and Berlin Institute of Health, Comprehensive Allergy-Centre, Department of Dermatology and Allergy, member of GA(2)LEN, Berlin, Germany.

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.
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http://dx.doi.org/10.1016/j.jaci.2019.06.049DOI Listing
January 2020

Will every child have allergic rhinitis soon?

Int J Pediatr Otorhinolaryngol 2019 Mar 18;118:53-58. Epub 2018 Dec 18.

Honorary Consultant Allergist & Rhinologist, RNTNE Hospital, University College Hospitals, London, United Kingdom. Electronic address:

Objectives: Given the increasing prevalence of AR amongst children, we aimed to review the literature regarding the future of AR in this population.

Methods: We searched the PubMed, Google and Proquest Central databases at Kırıkkale University Library. Search terms used were: "allergic rhinitis", "children", "paediatric", "allergy", "future", "risk factors", "treatment", "pharmacotherapy" and/or "allergen - specific immunotherapy". With regard to risk factors for allergic rhinitis, the terms "Environmental factors", "Improved hygiene", "Increased indoor allergen exposure", "Farms, villages, worms, and other parasites", "Environmental toxicants", "Diet", "Lifestyle changes", "Air pollution" and "Climate factors" were searched for. "Prevention of allergic diseases" and "Allergen-specific immunotherapy in the future" were also included in the search.

Results: AR has a high prevalence and causes considerable morbidity, has associated comorbidity and features specific complications. The principal treatments rely on avoiding the allergens responsible, and administering drug treatment or immunotherapy, which targets specific antigens. Genetic drift does not explain the rising prevalence of allergic disorders, but multifactorial environmental factors are likely culprits. Amongst such environmental factors to consider are the rise in caesarean births, decreases in breast feeding, dietary changes resulting in less fresh produce being consumed, the eradication of intestinal worm infestations, alterations in the way homes are aired and heated, children taking less exercise and being outdoors for shorter periods, whilst also having more contact with pollution.

Conclusion: Barring substantial lifestyle alterations, more and more children are likely to develop AR. It may prove feasible to stop allergy developing in the first place through manipulation of the microbiome, but the exact format such a modification should involve remains to be discovered. Molecular allergological techniques do offer the prospect of more precisely targeted immunotherapy, the sole disease modifier at present. However, at present the complexity and cost of such interventions prevents their widespread use and research in this area is still needed. The majority of children with AR are going to be managed using nasal saline sprays, since they are the most straightforward and least risky alternative for first line treatment.
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http://dx.doi.org/10.1016/j.ijporl.2018.12.019DOI Listing
March 2019

Chronic Rhinosinusitis-Could Phenotyping or Endotyping Aid Therapy?

Am J Rhinol Allergy 2019 Jan 24;33(1):83-93. Epub 2018 Oct 24.

4 Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, UK.

Objectives: We reviewed the phenotyping and endotyping of chronic rhinosinusitis (CRS) and treatment options.

Methods: We searched PubMed, Google, Google Scholar, and the Proquest Central Database of the Kırıkkale University Library.

Results: Phenotypes are observable properties of an organism produced by the environment acting upon the genotype, that is, patients with a particular disorder are subgrouped according to common characteristics. Currently, CRS is usually phenotyped as being with (CRSwNP) or without (CRSsNP) nasal polyps. However, this is not immutable as some individuals progress from nonpolyp to polypoid CRS over time. Phenotypes of CRS are also based on inflammatory patterns, generally CRSwNP is eosinophilic, CRSsNP neutrophilic; but there is a spectrum, rather than a clear-cut division into 2 types. An endotype is a subtype of a condition defined by a distinct functional or pathobiological mechanism. Endotypes of CRS can be (1) nontype Th2, (2) moderate type Th2, and (3) severe type Th2 immune reactions, based on cytokines and mediators such as IL4, 5, 13. CRS endotyping can also include a (1) type 2 cytokine-based approach, (2) eosinophil-mediated approach, (3) immunoglobulin E-based approach, and (4) cysteinyl leukotriene-based approach. Subdivisions of CRSwNP can be made into nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergic fungal sinusitis, and eosinophil pauci-granulomatous arteritis by testing. General treatment for all CRS is nasal douching. The place of surgery needs careful reconsideration. Endotype-directed therapies include glucocorticosteroids, antibiotics, aspirin, antifungals, anticytokines, and immunoglobulin replacement. The recognition of united airways and the co-occurrence of CRSwNPs and severe asthma should lead to common endotyping of both upper and lower airways in order to better direct therapy.

Conclusion: Endotyping can allow for the identification of groups of patients with CRS with a high likelihood of successful treatment, such as patients with a moderate type 2 immune reaction or those with acquired immune deficiency.
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http://dx.doi.org/10.1177/1945892418807590DOI Listing
January 2019

Legends of Allergy/ Immunology: Alfred William (Bill) Frankland.

Allergy 2019 02 22;74(2):380-381. Epub 2018 Oct 22.

Royal National TNE Hospital, London.

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http://dx.doi.org/10.1111/all.13612DOI Listing
February 2019

A Taste of Things to Come?

J Allergy Clin Immunol Pract 2018 May - Jun;6(3):1081-1082

Royal National Throat, Nose and Ear Hospital, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2017.09.006DOI Listing
September 2019

Case Report: Old World Mucosal Leishmaniasis: Report of Five Imported Cases to the Hospital for Tropical Diseases, London, United Kingdom.

Am J Trop Med Hyg 2017 Oct;97(4):1116-1119

Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, United Kingdom.

Old World species of typically cause visceral and cutaneous leishmaniasis. Mucosal involvement is typically seen with infection by species found in South America, usually after the healing of cutaneous leishmaniasis. We present five imported cases of mucosal leishmaniasis caused by Old World Mediterranean exclusively affecting the nasal mucosa or vocal cord. In only one case was there a recollection of a preceding cutaneous lesion compatible with cutaneous Leishmaniasis. Of significance was that four out of five cases were receiving local corticosteroids for chronic lung disorders and four were systemically immunosuppressed. This report highlights the importance of considering mucosal leishmaniasis in the differential diagnosis in those presenting with upper respiratory tract mucosal lesions with a relevant travel history to the Mediterranean and in whom malignancy has been excluded.
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http://dx.doi.org/10.4269/ajtmh.17-0162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637608PMC
October 2017

Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial.

J Allergy Clin Immunol 2017 Oct 4;140(4):1024-1031.e14. Epub 2017 Jul 4.

Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands.

Background: Patients with eosinophilic nasal polyposis frequently require surgery, and recurrence rates are high.

Objective: We sought to assess the efficacy and safety of mepolizumab versus placebo for severe bilateral nasal polyposis.

Methods: This randomized, double-blind, placebo-controlled trial recruited patients aged 18 to 70 years with recurrent nasal polyposis requiring surgery. Patients received 750 mg of intravenous mepolizumab or placebo every 4 weeks for a total of 6 doses in addition to daily topical corticosteroid treatment. The primary end point was the number of patients no longer requiring surgery at Week 25 based on a composite end point of endoscopic nasal polyp score and nasal polyposis severity visual analog scale (VAS) score. Secondary end points included change in nasal polyposis severity VAS score, endoscopic nasal polyp score, improvement in individual VAS symptoms (rhinorrhea, mucus in throat, nasal blockage, and sense of smell), patient-reported outcomes, and safety.

Results: One hundred five patients received mepolizumab (n = 54) or placebo (n = 51). A significantly greater proportion of patients in the mepolizumab group compared with the placebo group no longer required surgery at Week 25 (16 [30%] vs 5 [10%], respectively; P = .006). There was a significant improvement in nasal polyposis severity VAS score, endoscopic nasal polyp score, all individual VAS symptom scores, and Sino-Nasal Outcome Test patient-reported outcome score in the mepolizumab compared with placebo groups. Mepolizumab's safety profile was comparable with that of placebo.

Conclusion: In patients with recurrent nasal polyposis receiving topical corticosteroids who required surgery, mepolizumab treatment led to a greater reduction in the need for surgery and a greater improvement in symptoms than placebo.
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http://dx.doi.org/10.1016/j.jaci.2017.05.044DOI Listing
October 2017

MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis.

J Allergy Clin Immunol 2016 08 23;138(2):367-374.e2. Epub 2016 Apr 23.

Allergy-Centre-Charité at the Department of Dermatology, Charité-Universitätsmedizin Berlin, and Secretary General of the Global Allergy and Asthma European Network (GA(2)LEN), Berlin, Germany.

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.
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http://dx.doi.org/10.1016/j.jaci.2016.03.025DOI Listing
August 2016

Diagnosing Allergic Rhinitis.

Immunol Allergy Clin North Am 2016 May 26;36(2):249-60. Epub 2016 Feb 26.

Allergy, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK.

Allergic rhinitis (AR) is the most common immunologic disease in industrialized societies and has a significant impact on quality of life. Most asthmatics also have rhinitis. AR may present with comorbidities, including chronic otitis media with effusion, cough, and pollen-food cross-reactivity. AR may occur in isolation or be part of a mixed rhinitis.
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http://dx.doi.org/10.1016/j.iac.2015.12.003DOI Listing
May 2016

Peak nasal inspiratory flow and peak expiratory flow. Upright and sitting values in an adult population.

Rhinology 2016 Jun;54(2):160-3

Ear Institute, University College London, London, United Kingdom.

Background: Nasal obstruction is correlated with a decreased quality of life . An easy way to evaluate nasal patency is the peak nasal inspiratory flow (PNIF) measurement. Normal PNIF values have been published by many authors. However, some authors evaluated volunteers in a sitting position, while others have measured PNIF values in standing volunteers. Body position has been shown to influence pulmonary function, with differences between sitting and upright positions. As nasal and pulmonary flows are strictly related, the present pilot study tried to establish whether PNIF/PEF changed with body position in adults.

Methodology: PNIF and PEF were measured in sitting and standing positions with the order of testing randomized in 76 healthy volunteers, 30 male (40 ± 16 years).

Results: In the group as a whole between sitting and upright position, PEF was significantly different (p=0.009), while PNIF showed a trend towards a significant difference (p=0.10).

Conclusions: The present study, although showing a generally positive effect of the standing position on PEF values, does not show a clear effect on PNIF.
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http://dx.doi.org/10.4193/Rhin15.180DOI Listing
June 2016

Optimal management of allergic rhinitis.

Arch Dis Child 2015 Jun 2;100(6):576-82. Epub 2015 Apr 2.

Allergic rhinitis (AR), the most common chronic disease in childhood is often ignored, misdiagnosed and/or mistreated. Undertreated AR impairs quality of life, exacerbates asthma and is a major factor in asthma development. It can involve the nose itself, as well as the organs connected with the nose manifesting a variety of symptoms. Evidence-based guidelines for AR therapy improve disease control. Recently, paediatric AR guidelines have been published by the European Academy of Allergy and Clinical Immunology and are available online, as are a patient care pathway for children with AR and asthma from the Royal College of Paediatrics and Child Health. Management involves diagnosis, followed by avoidance of relevant allergens, with additional pharmacotherapy needed for most sufferers. This ranges, according to severity, from saline sprays, through non-sedating antihistamines, oral or topical, with minimally bioavailable intranasal corticosteroids for moderate/severe disease, possibly plus additional antihistamine or antileukotriene. The concept of rhinitis control is emerging, but there is no universally accepted definition. Where pharmacotherapy fails, allergen-specific immunotherapy, which is uniquely able to alter long-term disease outcomes, should be considered. The subcutaneous form (subcutaneous immunotherapy) in children has been underused because of concerns regarding safety and acceptability of injections. Sublingual immunotherapy is both efficacious and safe for grass pollen allergy. Further studies on other allergens in children are needed. Patient, carer and practitioner education into AR and its treatment are a vital part of management.
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http://dx.doi.org/10.1136/archdischild-2014-306300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514979PMC
June 2015

Laryngeal inflammation in the sudden infant death syndrome.

Curr Pediatr Rev 2014 ;10(4):309-13

Hon. Consultant Allergist & Rhinologist, RNTNE Hospital, London WC1X8DA, UK.

Objective: Sudden infant death syndrome (SIDS) is marked by 'the sudden death of an infant that is unexpected by history and remains unexplained after a thorough forensic autopsy and a detailed death scene investigation'. The cause is unknown. Excessive subglottic submucosal glandular tissue and excessive sulphated mucus glycoprotein in the larynges of SIDS babies have been previously reported from our institution. We now report on laryngeal immunohistology.

Methods: Larynges from 7 children who died from Sudden Infant Death Syndrome (SIDS) at under 16 weeks of age were examined immunohistologically and compared to those from 8 age- matched control infants who died from other causes.

Results: The SIDS babies had increased inflammatory changes in the laryngeal epithelium and sub- epithelium with raised numbers of cells staining for elastase (p<0.01), EG2(a marker for activated eosinophils) (p<0.01) and CD4(p<0.05) suggesting that some SIDS deaths involve preceding inflammation.

Conclusions: Although death may be sudden and unexpected it appears that, at least in some SIDS victims, there is a preceding inflammatory process in the larynx which may allow hyper-reactivity of laryngeal reflexes and consequent apnoea. This observation concurs with others in the SIDS literature and offers a field for further research and possible prevention.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428085PMC
http://dx.doi.org/10.2174/1573396311666150113213133DOI Listing
October 2015

Does the contraceptive pill influence peak nasal inspiratory flow values?

Rhinology 2014 12;52(4):355-9

Background: Early oral contraceptive pills (OCP) had higher estrogen levels and have been thought to cause nasal obstruction in about 40% of women users. A recent small study conducted on women taking OCP showed no significant effects on nasal patency. The aim of the present study was to analyse in a large number of volunteers if Peak Nasal Inspiratory Flow (PNIF) values could be influenced by modern OCP.

Methodology: PNIF was measured in 257 women (from 14 to 51 years old), divided into two groups: the study group composed of 109 healthy women taking modern OCP; the control group composed of 148 healthy women who did not take OCP. 9 women in the study group were excluded because of allergic disease, 248 females were finally considered. Data were statistically analysed and figures/tables were produced to see the effect of OCP on PNIF.

Results: The present study could not show any effect of OCP on nasal function. Moreover, while height influenced PNIF in both groups, age was not statistically significant.

Conclusion: From the present study, it seems that OCP could have no effects on nasal airflow, confirming that modern OCP with lower estrogen doses should not affect nasal mucosa or nasal patency.
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http://dx.doi.org/10.4193/Rhin14.004DOI Listing
December 2014

Audit of nasal lysine aspirin therapy in recalcitrant aspirin exacerbated respiratory disease.

World Allergy Organ J 2014 29;7(1):18. Epub 2014 Jul 29.

Department of Allergy & Rhinology, Royal National Throat, Nose and Ear Hospital, ,330 Grays Inn Road, London WC1X8DA, UK.

Background: Aspirin - exacerbated respiratory disease can prove difficult to control. Oral aspirin desensitization is effective, but has adverse effects and may not be cardio-protective at the high doses needed.

Objective: To examine the effectiveness of aspirin administered in lower doses via the nose.

Methods: An audit of 121 patients with aspirin exacerbated respiratory disease (AERD), 105 of whom were treated with intranasal lysine aspirin in gradually increasing doses following positive lysine aspirin challenge.

Results: Treatment was associated with subjective symptomatic improvement or stabilization in 60 of 78 patients at 3 months and 19 of 27 at 12 months. Nasal inspiratory peak flow, olfaction, exhaled and nasal nitric oxide levels were significantly improved (p < 0.05 for all). Patients with positive skin prick tests and those with later onset (>40 years) AERD improved more than non-atopics and those with early onset AERD. Asthma outcomes over 1 year were assessed by questionnaire in 22 patients on lysine aspirin and in 20 who were positive on challenge but who either refused treatment or took it only briefly (less than or equal to 3 months). There was a significant decrease in emergency visits (p = 0.0182), hospitalization (p = 0.0074) and oral steroid use (p = 0.004) in those on nasal lysine aspirin for a year. Gastrointestinal side effects occurred in 3.8%, lower than those reported for oral aspirin therapy. Conclusions and Clinical Relevance This form of therapy might reduce the need for expensive monoclonal antibodies in AERD patients.
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http://dx.doi.org/10.1186/1939-4551-7-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114086PMC
August 2014

Topical nasal lysine aspirin in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis with nasal polyposis.

Expert Rev Clin Immunol 2014 May 31;10(5):657-65. Epub 2014 Mar 31.

Imperial College Healthcare NHS Trust, St. Mary's Hospital, Praed Street, London W2 1NY, UK.

Chronic rhinosinusitis patients with nasal polyps can be aspirin sensitive or aspirin tolerant. The majority belong to the latter group. They tolerate intake of aspirin or other non-steroidal anti-inflammatory drugs, whereas aspirin-sensitive patients have an adverse reaction (asthma, rhinitis and/or urticaria). Diagnosis of aspirin sensitivity is important for the patient, but is rarely undertaken in routine ENT or respiratory medicine practice. Treatment of nasal polyps is by a combination of medical therapy and surgery. Oral and topical steroids form the mainstay of medical therapy, which is aimed at reducing inflammation and symptom improvement. Surgery helps with polyps causing severe nasal obstruction. Despite these therapies, recurrences are common in aspirin sensitive patients. Any adjunctive therapy to prevent or prolong recurrence would be welcome. One such possibility is topical nasal lysine-aspirin. This is an area under current debate and this non-systematic review aims to provide evidence of its use, to date, in aspirin sensitive and aspirin tolerant nasal polyp patients.
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http://dx.doi.org/10.1586/1744666X.2014.901889DOI Listing
May 2014

Unilateral peak nasal inspiratory flow, normal values in adult population.

Rhinology 2012 Dec;50(4):386-92

Department of Neurosciences, Otolaryngology Section, University of Padova, Padova, Italy.

Aims: Measurement of Peak Nasal Inspiratory Flow (PNIF) is a cheap, simple, easily performed method to assess nasal patency and it is suitable for serial measurements and for home use. The purpose of this study was to establish normative unilateral PNIF data for a healthy adult population and provide charts relating unilateral PNIF normal values with various explanatory variables.

Methods And Results: Repeated measurements of PNIF and unilateral PNIF were performed in 109 volunteers. Ninety seven of these fulfilled the study criteria and all of them were non-smokers, non-asthmatic, without nose and paranasal sinus problems, with ages ranging from 13 to 80 years. Data were statistically analysed and tables were produced relating unilateral PNIF to height which was the only studied variable that correlated statistically with unilateral PNIF.

Conclusions: The measurement of unilateral PNIF, providing the present data are confirmed in a larger series, could be a useful method to study single nostril patency to aid diagnosis of nasal disease, especially when it is necessary to assess the functional effects of unilateral nasal septal deviations or in all cases where there is a suspicion of a unilateral nasal occlusion. This pilot study provides initial normative unilateral PNIF data.
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http://dx.doi.org/10.4193/Rhino12.071DOI Listing
December 2012

Should intranasal corticosteroids be used for the treatment of ocular symptoms of allergic rhinoconjunctivitis? A review of their efficacy and safety profile.

Int Arch Allergy Immunol 2012 4;158(4):317-25. Epub 2012 Apr 4.

Institute of Ophthalmology, University College London, and Moorfields Eye Hospital, London, UK.

Allergic rhinoconjunctivitis (ARC) presents as nasal symptoms, eye watering and additional signs of ocular allergy (e.g. itchy/burning eyes). Intranasal corticosteroids (INSs) are the most effective treatment for the nasal symptoms of seasonal allergic rhinitis (SAR; based on 4 meta-analyses) and are considered first-line therapy when nasal congestion forms a substantial component of the patient's rhinitis symptoms. Clinical trial evidence shows that INSs also provide some relief from ocular symptoms of SAR and seasonal ARC in adults. INSs probably alleviate eye watering, the main ocular symptom of SAR, by relieving nasal congestion. Other ocular symptoms also improve with INSs. The mechanism for this effect is unknown, but might relate to naso-ocular reflex reduction. There are limited data on ocular safety with INSs. However, the literature supports the use of INSs over several months as there appears to be no considerable increase in the risk of ocular hypertension or glaucoma.
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http://dx.doi.org/10.1159/000333100DOI Listing
September 2012

SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial.

J Allergy Clin Immunol 2012 Mar 29;129(3):717-725.e5. Epub 2012 Jan 29.

Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College and Royal Brompton Hospital, London, United Kingdom.

Background: The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials.

Objective: To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU,(∗) ALK, Denmark) or placebo.

Methods: A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters.

Results: The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% (P ≤ .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by 20% to 45% (P ≤ .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% (P ≤ .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% (P ≤ .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified.

Conclusion: The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis.
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http://dx.doi.org/10.1016/j.jaci.2011.12.973DOI Listing
March 2012

Chronic rhinosinusitis: therapeutic efficacy of anti-inflammatory and antibiotic approaches.

Allergy Asthma Immunol Res 2011 Oct 1;3(4):226-35. Epub 2011 Sep 1.

Department of Allergy and Medical Rhinology, Royal National Throat Nose Ear Hospital London, University College London, London, UK.

Despite the high prevalence of chronic rhinosinusitis (CRS) worldwide, the exact pathogenesis of the disease remains unknown. Even with therapeutic intervention, treatment response is often only partial and frequently ineffective. The inability to define exact disease phenotypes in relation to specific disease mechanisms has led to a broad based approach with both anti-inflammatory and anti-microbial intervention. The clinical efficacy of such current therapeutic strategies is highlighted and the urgent need for further robust therapeutic intervention studies in CRS is discussed in this article.
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http://dx.doi.org/10.4168/aair.2011.3.4.226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178820PMC
October 2011

Allergic rhinitis.

Lancet 2011 Dec 23;378(9809):2112-22. Epub 2011 Jul 23.

Asthma and Allergy Centre, San Diego, CA, USA.

Allergic rhinitis is a very common disorder that affects people of all ages, peaking in the teenage years. It is frequently ignored, underdiagnosed, misdiagnosed, and mistreated, which not only is detrimental to health but also has societal costs. Although allergic rhinitis is not a serious illness, it is clinically relevant because it underlies many complications, is a major risk factor for poor asthma control, and affects quality of life and productivity at work or school. Management of allergic rhinitis is best when directed by guidelines. A diagnostic trial of a pharmacotherapeutic agent could be started in people with clinically identified allergic rhinitis; however, to confirm the diagnosis, specific IgE reactivity needs to be recorded. Documented IgE reactivity has the added benefit of guiding implementation of environmental controls, which could substantially ameliorate symptoms of allergic rhinitis and might prevent development of asthma, especially in an occupational setting. Many classes of drug are available, effective, and safe. In meta-analyses, intranasal corticosteroids are superior to other treatments, have a good safety profile, and treat all symptoms of allergic rhinitis effectively. First-generation antihistamines are associated with sedation, psychomotor retardation, and reduced academic performance. Only immunotherapy with individually targeted allergens has the potential to alter the natural history of allergic rhinitis. Patients' education is a vital component of treatment. Even with the best pharmacotherapy, one in five affected individuals remains highly symptomatic, and further research is needed in this area.
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http://dx.doi.org/10.1016/S0140-6736(11)60130-XDOI Listing
December 2011

Atopic myelitis in a European woman residing in Japan.

J Neurol Neurosurg Psychiatry 2011 Sep 14;82(9):1022-4. Epub 2010 Aug 14.

National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.

Nearly 100 cases of atopic myelitis have been reported in Japan. However, it has only been described in two non-Japanese patients, both from Western Europe. We report a European individual who developed cervical myelitis while resident in Japan. This showed a partial response to corticosteroids. There was no clinical or radiological dissemination for over 5 years, at which time she had a brainstem relapse caused by a new lesion in the medulla oblongata. The patient had high serum total IgE with evidence of allergy to several antigens, including house dust mite and soya. It is possible that the incidence of atopic myelitis may be underestimated where it is not standard practice to measure serum IgE levels in patients with myelopathy. Such cases will instead be subsumed into the diagnostic category of clinically isolated syndrome. However, it remains uncertain whether atopic myelitis is a distinct disease or falls within the spectrum of demyelinating diseases. Further studies are required to fully elucidate the relationship between atopy and the incidence and severity of CNS inflammatory disorders.
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http://dx.doi.org/10.1136/jnnp.2009.186775DOI Listing
September 2011

Recent advances in antileukotriene therapy.

Curr Opin Allergy Clin Immunol 2010 Aug;10(4):370-6

Department of Allergy and Clinical Immunology, Imperial College, London, UK.

Purpose Of Review: Despite profound effects of leukotrienes in experimental models, clinical responses to antileukotriene drugs are highly heterogeneous. This review discusses recent advances concerning the molecular mechanisms of antileukotrienes as well as their efficacy in various clinical scenarios and patient groups.

Recent Findings: Appreciation of the role of leukotriene E4 and the existence of its distinct receptors may explain the limited efficacy of current leukotriene receptor antagonists. Pharmacogenetic studies highlight the influence of several leukotriene pathway genes on clinical responsiveness. Benefits of addition of antileukotrienes to inhaled corticosteroids in chronic adult asthmatics have been shown, but their role in acute asthma is unclear. Evidence suggests they are not a first-line treatment for allergic rhinitis or urticaria, but may provide useful additional therapy. In children antileukotrienes provide symptomatic benefit in preschool wheezers, but have no clear role in bronchiolitis or acute asthma. Adherence to montelukast appears superior to inhaled corticosteroids. Use in sleep-disordered breathing and eosinophilic gastroenteropathies warrants further investigation. Despite recent concerns thorough analysis of existing data suggests antileukotrienes are well tolerated drugs. The possible link with Churg-Strauss syndrome requires further investigation.

Summary: The leukotriene pathway remains an attractive target in asthma and allergic disease, particularly in light of renewed appreciation of the role of leukotriene E4. Clarification of the clinical role of antileukotrienes is needed.
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http://dx.doi.org/10.1097/ACI.0b013e32833bfa20DOI Listing
August 2010

Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet.

J Allergy Clin Immunol 2010 Jan;125(1):131-8.e1-7

Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College and Royal Brompton Hospital, Guy Scadding Building, Royal Brompton Campus, Dovehouse St, SW3 6LY London, United Kingdom.

Background: Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial.

Objective: We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abelló, Hørsholm, Denmark).

Methods: A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events.

Results: Significant improvements in efficacy were consistently shown during 3 years' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified.

Conclusion: Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment, which is indicative of disease modification and associated long-term benefits.
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http://dx.doi.org/10.1016/j.jaci.2009.10.035DOI Listing
January 2010