(A) Allergy prelims 12/5/06 16:50 Page iii T H E Y E A R I N A L L E RG Y VO L U M E 3 EDITED BY S HASAN ARSHAD AND STEPHEN T HOLGATE CLINICAL PUBLISHING OXFORD (A) Allergy prelims 12/5/06 16:50 Page iv Clinical Publishing an imprint of Atlas Medical Publishing Ltd Oxford Centre for Innovation Mill Street, Oxford OX2 0JX, UK Tel: +44 1865 811116 Fax: +44 1865 251550 E mail: [email protected] Web: www.clinicalpublishing.co.uk Distributed by: Marston Book Services Ltd PO Box 269 Abingdon Oxon OX14 4YN, UK Tel: +44 1235 465500 Fax: +44 1235 465555 E mail: [email protected] © Atlas Medical Publishing Ltd 2006 First published 2006 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Clinical Publishing or Atlas Medical Publishing Ltd Although every effort has been made to ensure that all owners of copyright material have been acknowledged in this publication, we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention A catalogue record for this book is available from the British Library ISBN 1 904392 60 1 Electronic ISBN 978 1 84692 562 7 ISSN 1477-8106 The publisher makes no representation, express or implied, that the dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publisher do not accept any liability for any errors in the text or for the misuse or misapplication of material in this work Project Manager: Rosemary Osmond, Helimetrics Ltd, Chipping Norton, Oxon, UK Typeset by Hope Services (Abingdon) Ltd, Abingdon, Oxon, UK Printed by T G Hostench SA, Barcelona, Spain (A) Allergy prelims 12/5/06 16:50 Page v Contents Editors and contributors vii Foreword ix Preface xi Part I Epidemiology and genetics 1. Epidemiology and risk factors 3 Wilfried Karmaus 2. Genetics of asthma and allergy 19 Susan Ewart Part II Pathophysiology and diseases 3. Airway inflammation 45 Gordon Dent 4. Atopic dermatitis 71 Hasan Arshad 5. Allergic rhinitis 91 Hasan Abid 6. Systemic allergic reactions 111 Graham Roberts 7. Food allergy 129 Taraneh Dean 8. Drug allergy 147 John Mucklow 9. Immunodeficiency 171 Richard Baretto, Sarah Goddard, Aarnoud Huisson, Mamidipudi T Krishna (A) Allergy prelims 22/5/06 11:52 Page vi VI CONTENTS Part III Treatment modalities for allergic diseases 10. Environment control 193 Hasan Arshad 11. Immunotherapy 213 Anthony Williams, Richard Baretto, Mamidipudi T Krishna 12. Bronchodilators (including PDE-4 inhibitors) 231 Brett Pereira 13. Corticosteroids and asthma 245 Suresh Babu, Jaymin Morjaria 14. Experimental therapies for allergic disorders 269 Jaymin Morjaria, Suresh Babu 15. Other therapies (antihistamines,leukotriene modifiers, calcineurin inhibitors,anti-lgE) 285 Brett Pereira Acronyms/abbreviations 305 Index ofpapers reviewed 309 General index 323 (A) Allergy prelims 12/5/06 16:50 Page vii Editors S Hasan Arshad, DM, FRCP Senior Lecturer in Respiratory Medicine and Allergy,Schools ofMedicine and Life Sciences,Keele University,Keele,Staffordshire,UK Stephen T Holgate, DSC, FRCP Medical Research Council Clinical Professor ofImmunopharmacology,School of Medicine,University ofSouthampton,Southampton,UK Contributors S Hasan Abid, FCPS Associate Professor,Department ofOtolaryngology,Dow University ofMedical Sciences,Karachi,Pakistan S Hasan Arshad, DM, FRCP Senior Lecturer in Respiratory Medicine and Allergy,Schools ofMedicine and Life Sciences,Keele University,Keele,Staffordshire,UK K Suresh Babu, DM Research Fellow,Southampton General Hospital,Southampton,UK Richard L Baretto, PHD, MRCP, MRCPATH Consultant Immunologist,Department ofImmunology,Leicester Royal Infirmary,Leicester,UK Taraneh Dean, PHD Reader in Epidemiology,School ofHealth Sciences and Social Work,University of Portsmouth,Portsmouth,UK Gordon Dent, PHD Lecturer in Pharmacology,Institute ofScience and Technology in Medicine,Keele University,Keele,Staffordshire,UK Susan Ewart, PHD Associate Professor ofGenetics,Michigan State University,East Lansing, Michigan,USA (A) Allergy prelims 12/5/06 16:50 Page viii VIII CONTRIBUTORS Sarah Goddard, PHD, MRCP, DIP RCPATH Specialist Registrar,Department ofImmunology,Birmingham Heartlands Hospital,Birmingham,UK Aarnoud Huissoon, PHD, MRCP(I), MRCPATH Consultant Immunologist and Honorary Senior Clinical Lecturer,Department of Immunology,Birmingham Heartlands Hospital,Birmingham,UK Wilfried Karmaus, MD, DR.MED, MPH Professor ofEpidemiology,University ofSouth Carolina,Columbia,South Carolina,USA Mamidipudi Thirumala Krishna, PHD, FRCP, MRCPATH Consultant Immunologist and Honorary Senior Clinical lecturer,Department of Immunology,Birmingham Heartlands Hospital,Birmingham,UK Jaymin Morjaria, MD, MRCP Research Fellow,Southampton General Hospital,Southampton,UK John Mucklow, MD, FRCP, FBPHARMACOLS, DIPMEDED Consultant Physician,Department ofClinical Pharmacology,University Hospital ofNorth Staffordshire,Stoke-on-Trent,UK Brett Pereira, MD, MRCP Consultant Physician,Department ofRespiratory Medicine,Kent and Canterbury Hospital,Canterbury,Kent,UK Graham Roberts, DM, MSC, MRCPCH Clinical Senior Lecturer,Paediatric Allergy and Respiratory Medicine,School of Medicine,University ofSouthampton,Southampton,UK Anthony P Williams, PHD, MRCP, MRCPATH Wellcome Trust Clinician Scientist and Honorary Consultant Immunologist, University ofSouthampton and Department ofImmunology,Southampton General Hospital,Southampton,UK (A) Allergy prelims 22/5/06 11:52 Page ix Foreword N FRANKLINADKINSONJR, MD Professor of Medicine and Allergy Immunology Training Program Director Johns Hopkins Asthma and Allergy Center Baltimore, Maryland, USA In this ‘information age’ofmedicine,researchers and practitioners have easy access electronically to an ever-increasing portfolio of original research and practice guidelines.Finding recent literature pertinent to almost any medical problem is a skill now taught to most medical students,and definitively in post-doctoral med- ical education.Finding time to read and digest all we can locate and retrieve with ease is a bigger challenge,but not the biggest one. After finding and reading a new paper,especially one involving original research, the important facility is the ability to place it in proper context with what has come before.To some degree,authors address this chore in the ‘introduction’and ‘discus- sion’section of their papers.But with increasing frequency,authors are not fully aware of the significance (or lack thereof) of their work, the determination of which may require consideration of post-publications dialogues, editorials and public reactions,and integration with what others know is ‘in press’or underway. So the optimal time for trying to assess the merits and heuristic value of pub- lished works may be in the year following its publication,preferably by knowledge- able and unbiased observers who are monitoring the ‘bigger picture.’Enter now the third volume of The Year in Allergy which accomplishes this task admirably for those whose eyes need to be focused on the origins,pathophysiology and treatment ofallergic diseases.The authors,backed by skilful editorial oversight,have success- fully reviewed some of the most important papers dealing with allergy published over the past eighteen months,and put them into proper perspective scientifically and in most cases clinically as well. Key figures and tables highlight the most important quantitative findings.The Commentsections identify the significance of the work and its relationship to previous similar observations,and in some cases to theories under examination.And then each abstracting section author has written a conclusion which attempts to assess what ‘progress’has been noted in the topic area in the recent past,and what obstacles are now impeding needed insights or data collection. All in all,this is a wonderfully stimulating way to review recent reports in each ofthe major areas ofallergic disorders and to get some sense ofhow the field may have been moved forward in the past year.What I have also found is that these cogent commentaries have primed me appropriately to read new papers coming along with a better sense of importance and potential contribution to the field.I (A) Allergy prelims 12/5/06 16:50 Page x X FOREWORD congratulate the Editors on achieving their educational objective, and commend this book to trainees and experts alike, and to both investigators and clinicians. Increasingly,I see efforts like this volume as one of the most fruitful formats for ongoing medical education. (A) Allergy prelims 12/5/06 16:50 Page xi Preface STEPHENT HOLGATE, DSC, FRCP Medical Research Council Clinical Professor of Immunopharmacology School of Medicine University of Southampton Southampton UK The Year in Allergyseries is proving to be a very popular source of recent research findings in allergy.This is the third volume in the series and draws on a research lit- erature over the last 2 years.We have divided the book into 3 main sections with individual subjects within each section dealt with separately.While the concept of allergy has been well accepted since the days ofCharles Blackley who first described hay fever or hay asthma (catarrhus aestevus) in 1880,and Karl Prausnitz and his assistant Heinz Kustner who are remembered for the first demonstration in humans ofreagin (later to be identified as IgE) in 1921,progress since has been rel- atively slow in determining the role ofatopy in disease pathogenesis.Over the last decade, however, there has been an explosion of interest in immunology and immunopharmacology underlying the allergic process through engagement of both B and T lymphocytes and antigen-presenting cells and their subsets involved in subverting the immune response towards an allergic state.The identification of individual chemical substances that contribute to the pathophysiological events of an allergic response has also provided fertile ground for new discovery including the development of novel H -antihistamines and cysteinyl leukotriene receptor 1 antagonists. The clear recognition that all allergic disease and the general state of atopy is progressively increasing in its incidence worldwide in relation to the adoption ofa Western-type lifestyle has raised allergy as a public health problem.A better under- standing ofthe cell and molecular basis ofallergic mechanisms linked to carefully conducted environmental epidemiology has led to a range ofnew ideas that might explain these rising trends.In this edition ofThe Year in Allergythere are some new publications that provide a basis for why these diseases are becoming more preva- lent and what the underlying environmental factors might be. Allergic diseases, including rhinitis, asthma, food and insect allergy, and atopic dermatitis, are all complex disorders with both environmental and genetic factors playing important roles.The development ofmodern genetic epidemiology and new ways ofexplor- ing human genetics and epigenetics (gene–gene and gene–environment interac- tions) in complex disease is leading to the discovery of novel molecules,hitherto never thought to be involved in disease mechanisms, let alone allergic disease. Several examples of these are given in this volume including consideration of gene–environmental interactions.