ERS Annual Congress Munich 6–10 September 2014 Postgraduate Course 15 Hot topics in paediatric allergy Saturday, 6 September 2014 14:00–17:30 Room M-1 (B0) You can access an electronic copy of these educational materials here: www.ers-education.org/2014pg15 To access the educational materials on your tablet or smartphone please find below a list of apps to access, annotate, store and share pdf documents. iPhone / iPad Adobe Reader - FREE With the Adobe Reader app you can highlight, strikethrough, underline, draw (freehand), comment (sticky notes) and add text to pdf documents using the typewriter tool. It can also be used to fill out forms and electronically sign documents. http://bit.ly/1sTSxn3 UPAD Lite - FREE UPAD Lite is an advanced note-taking application with annotation features. You can handwrite notes, highlight text, add sticky notes and reference images and export any type of document as a PDF or PNG file by email or to cloud services. http://bit.ly/1mQ1j0K Noteability - $4.99 Noteability uses CloudServices to import and automatically backup your PDF files and allows you to annotate and organise them (incl. special features such as adding a video file). On iPad, you can bookmark pages of a note, filter a PDF by annotated pages, or search your note for a keyword. http://bit.ly/TCrNad Android Adobe Reader - FREE The Android version of Adobe Reader lets you view, annotate, comment, fill out, electronically sign and share documents. It has all of the same features as the iOS app like freehand drawing, highlighting, underlining, etc. http://bit.ly/1deKmcL iAnnotate PDF - FREE You can open multiple PDFs using tabs, highlight the text and make comments via handwriting or typewriter tools. iAnnotate PDF also supports Box OneCloud, which allows you to import and export files directly from/to Box. http://bit.ly/1p2SV00 ez PDF Reader - $3.99 With the ez PDF reader you can add text in text boxes and sticky notes; highlight, underline, or strikethrough texts or add freehand drawings. Add memo & append images, change colour / thickness, resize and move them around as you like. http://bit.ly/1kdxZfT Postgraduate Course 15 Hot topics in paediatric allergy AIMS: Asthma and allergies are the most prevalent chronic disorders in children in the western world. In this postgraduate course, experts in the field will discuss the recent advances in four major areas within paediatric allergy, namely, allergic skin diseases, food allergy, anaphylaxis, and drug allergies, in an interactive, case-based manner. HERMES LINKS PAEDIATRIC: Allergic Disorders, Bronchial Asthma and other wheezing disorders. TARGET AUDIENCE: Pulmonologists, respiratory physicians, general practitioners, nurses, allergologists, and trainees. CHAIRS: N. Arends (Rotterdam, Netherlands), A. Barbato (Padova, Italy) COURSE PROGRAMME PAGE 14:00 Preschool wheeze: what is new since the 2008 taskforce? 5 P.L.P. Brand (Zwolle, Netherlands) 14:45 An update on food allergy 38 K. Beyer (Berlin, Germany) 15:30 Break 16:00 Paediatric drug allergy: state of the art 39 M. Duse (Rome, Italy) 16:45 Anaphylaxis in children 43 G. Roberts (Southampton, United Kingdom) Additional course resources 82 Faculty disclosures 83 Faculty contact information 84 Answers to evaluation questions 85 THE ERS HANDBOOK OF paediatric respiratory medicine Th e ERS Handbook of Paediatric Respiratory Medicine Edited by Ernst Eber and Fabio Midulla ISBN 978-1-84984-038-5 ERS Handbook of Paediatric Respiratory Medicine Th e comprises more than 100 sections covering the whole spectrum of paediatric respiratory medicine, from anatomy and development to disease, rehabilitation and treatment. Th e book is structured to tie in with the paediatric HERMES syllabus, making it an essential resource for anyone interested in the fi eld and the ideal training aid for those wishing to take the European Examination in Paediatric Respiratory Medicine. Accredited by EBAP for 18 hours of European CME credit To buy printed copies, visit the ERS Bookshop in Hall A1, stand D.01. Visit ersbookshop.com Preschool wheeze: what is new since the 2008 taskforce? Prof. Paul L.P. Brand Consultant paediatrician for respiratory and allergic disease Princess Amalia Children’s Clinic Isala Klinieken P.O. Box 10400 8000 GK Zwolle Netherlands [email protected] Twitter @paulbrandzwolle AIMS • To discuss limitations of distinguishing episodic viral wheeze and multiple trigger wheeze. • To provide evidence based treatment recommendations for preschool children with troublesome recurrent wheeze. SUMMARY Introduction Wheezing and shortness of breath are very common presenting symptoms in preschool children. Approximately one in three children has at least one episode of wheeze before their third birthday.[1;2] Parents vary considerably in their understanding of the term ‘‘wheeze’’ but wheeze confirmed by a doctor is associated with lower airway obstruction.[3] Even among such children with doctor-confirmed wheeze, considerable clinical heterogeneity exists: children differ considerably in the severity and frequency of wheeze episodes, and in other clinical characteristics. Due to this heterogeneity, and despite its common occurrence, relatively little evidence is available on the pathophysiology and treatment of wheezing in preschool children. Many preschool children with wheeze become symptom-free between the ages of 3 and 8 years .[4] This distinguishes preschool wheeze from the more persistent asthma in later childhood and adulthood, and illustrates the heterogeneity of wheeze in this age group. Until recently, however, international asthma management guidelines did notprovide separate recommendations for preschool children. In 2008, a European Respiratory Society (ERS) Task Force published a report on the classification, diagnosis and management of preschool wheeze, based on a systematic assessment of the available literature at that time.[5] One of the Task Force’s main findings was that ‘‘the evidence on which to base recommendations is limited’’ and that ‘‘The present recommendations are likely to change when more evidence becomes available.’’ In 2008, the Task Force recommended distinguishing between episodic viral wheeze (EVW, wheeze only during or following a viral cold) and multiple trigger wheeze (MTW, wheeze not only in response to viral colds, but also to other triggers) and proposed a differentiated approach to controller therapy (montelukast as first choice treatment for EVW and inhaled corticosteroids (ICS) for MTW).[5] Since 2008, a large number of studies have provided important new evidence which necessitate a reconsideration of the ERS 2008 Task Force recommendations. Because of this, an international group of experts convened at the 2013 ERS Annual Congress to discuss the current state of the art of the classification and management of preschool wheeze, and to formulate a consensus statement on the current value of phenotyping preschool wheezing disorders into EVW and MTW, and the treatment approach associated with it. The group’s report was recently published in the ERJ, and the highlights of this report will be discussed in this presentation.[6] 5 Classification The 2014 update of the ERS Task Force Report recognizes that the distinction between EVW and MTW is not as clear-cut, and not as clinically useful, as was proposed in 2008. There are two main reasons for this paradigm shift. First, it was recognized that the temporal pattern of wheeze in relation to triggers (i.e., EVW or MTW) was not the only characteristic that varies between preschool children with wheeze (table 1).[6]In clinical practice, the severity and frequency of wheeze episodes are more important in determining whether a child will be prescribed daily controller therapy than whether the wheeze follows an EVW or MTW pattern. Clinicians also weigh other factors into this decision, such as the presence of allergic comorbidity (eczema, allergic rhinitis, food allergy), and the patient’s family history.[7] Table 1: reproduced from [6] Second, it has been shown that the EVW and MTW phenotypes are not stable over time in many patients.[8] For example, in a cohort of 109 preschool children followed for one year in an Australian children’s hospital (indicating that these were children with relatively severe wheeze who were referred for specialist care), only 50 (46%) had a stable MTW or EVW phenotype. Thirty-five patients (32%) changed from an EVW to an MTW phenotype or vice versa, and 24 (22%) became wheeze-free during daily controller therapy.[8] This unstability of wheeze phenotypes over time limit sits usefulness for classification purposes and as a basis for prescription of therapy. This is reflected in the 2014 update of the ERS Task Force Report.[6] Treatment The 2008 ERS Task Force Report recommendation for phenotype-directed choice of daily controller therapy was based on limited evidence, with only one randomized controlled trial (RCT) showing a significant, but small, reduction of wheeze symptoms in preschool children treated with montelukast,[9] and a single negative RCT in preschool children with an EVW phenotype.[10] A systematic review of 16 ICS RCTs in preschool children showed a significant and clinically relevant reduction of wheeze episodes and severity in the pooled meta-analysis.[11] Because phenotype descriptions were missing in most of these studies, it was not possible to do a stratified analysis based on wheeze phenotype. To date, a single study has compared ICS to montelukast in preschool children, showing superiority of budesonide (an ICS) over montelukast daily controller therapy.[12] A recent study in the Netherlands showed that adherence to daily ICS controller therapy was the single most important factor in determining asthma control in preschool children followed for one year using electronic assessment of adherence.[13] These observations suggest that ICS daily controller therapy is useful and effective in preschool children with wheeze of sufficient severity to merit referral to a hospital-based paediatric specialist. The 2014 update of the ERS Task Force Report therefore proposes that ICS be used as daily controller therapy not only in children with the MTW phenotype, but also in those children with EVW who have severe or frequent episodes, or when the clinician suspects that interval symptoms are being underreported.[6] Given the favourable natural history of preschool wheezing (at population level, the majority of preschool children with wheeze become symptom-free after the age of 4-6 years), any maintenance treatment should be viewed as a treatment trial, with scheduled follow-up. Daily controller therapy should be tapered down to the lowest effective dose, and should be discontinued when the patient has remained symptom-free for 3-6 months.[6] It should be 6 stressed, however, that the favourable history of preschool wheezing has been primarily demonstrated in population-based samples, in which most wheezy children have mild symptoms. Surprisingly few data are available on the long-term outcome of preschool wheezing in children with more severe symptoms, who have been referred to specialist care. In a recent follow-up study of such patients with troublesome EVW, 67% of children remained symptomatic by the age of 5-10 years.[14] Unfortunately, currently available scoring systems are too unreliable to allow meaningful prediction of long-term outcome and treatment response to allow targeted presciption of daily controller therapy.[15] Daily controller therapy of preschool wheezing does not influence the long-term outcome of preschool wheeze, but does reduce troublesome symptoms during the preschool age period. This is why preschool children with recurrent troublesome symptoms deserve a trial of daily controller therapy. REFERENCES 1. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ, Group Health Medical Associates: Asthma and wheezing in the first six years of life. N Engl J Med 1995;332:133-138. 2. Henderson J, Granell R, Heron J, Sherriff A, Simpson A, Woodcock A, Strachan DP, Shaheen SO, Sterne JA: Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax 2008;63:974-980. 3. Lowe L, Murray CS, Martin L, Deas J, Cashin E, Poletti G, Simpson A, Woodcock A, Custovic A: Reported versus confirmed wheeze and lung function in early life. Arch Dis Child 2004;89:540-543. 4. Savenije OE, Kerkhof M, Koppelman GH, Postma DS: Predicting who will have asthma at school age among preschool children. J Allergy Clin Immunol 2012;130:325-331. 5. Brand PL, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A, de Blic J, de Jongste JC, Eber E, Everard ML, Frey U, Gappa M, Garcia-Marcos L, Grigg J, Lenney W, Le Souef P, McKenzie S, Merkus PJ, Midulla F, Paton JY, Piacentini G, Pohunek P, Rossi GA, Seddon P, Silverman M, Sly PD, Stick S, Valiulis A, Van Aalderen WM, Wildhaber JH, Wennergren G, Wilson N, Zivkovic Z, Bush A: Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J 2008;32:1096-1110. 6. Brand PL, Caudri D, Eber E, Gaillard EA, Garcia-Marcos L, Hedlin G, Henderson J, Kuehni CE, Merkus PJ, Pedersen S, Valiulis A, Wennergren G, Bush A: Classification and pharmacological treatment of preschool wheezing: changes since 2008. Eur Respir J 2014;43:1172-1177. 7. Schultz A, Brand PL: Episodic Viral Wheeze and Multiple Trigger Wheeze in preschool children: A useful distinction for clinicians? Paediatr Respir Rev 2011;12:160-164. 8. Schultz A, Devadason SG, Savenije OE, Sly PD, Le Souef PN, Brand PL: The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze. Acta Paediatr 2010;99:56-60. 9. Bisgaard H, Zielen S, Garcia-Garcia ML, Johnston SL, Gilles L, Menten J, Tozzi CA, Polos P: Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma. Am J Respir Crit Care Med 2005;171:315-322. 10. Wilson N, Sloper K, Silverman M: Effect of continuous treatment with topical corticosteroid on episodic viral wheeze in preschool children. Arch Dis Child 1995;72:317-320. 11. Castro-Rodriguez JA, Rodrigo GJ: Efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing and asthma: a systematic review with meta-analysis. Pediatrics 2009;123:e519-e525. 12. Szefler SJ, Carlsson LG, Uryniak T, Baker JW: Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma. J Allergy Clin Immunol Pract 2013;1:58-64. 7 13. Klok T, Kaptein AA, Duiverman EJ, Brand PL: It's the adherence, stupid (that determines asthma control in preschool children)! Eur Respir J 2014;43:783-791. 14. Kappelle L, Brand PL: Severe episodic viral wheeze in preschool children: High risk of asthma at age 5-10 years. Eur J Pediatr 2012;171:947-954. 15. Fouzas S, Brand PL: Predicting persistence of asthma in preschool wheezers: crystal balls or muddy waters? Paediatr Respir Rev 2013;14:48-52. EVALUATION 1. Which of the following statements is true? I. >50% of preschool children with episodic viral wheeze referred to hospital based paediatric care become symptom free by the age of 6 years. II. Episodic viral wheeze does not respond to inhaled corrticosteroids maintenance treatment. a. Both statements are true. b. Statement I is false, statement II is true. c. Statement I is true, statement II is false. d. Both statements are false. 2. Which of the following statements is true? I. >25% of preschool children with wheeze change phenotype from EVW to MTW or vice versa within one year. II. The severity and frequency of wheeze episodes are less important than the wheeze pattern (EVW or MTW) in determining the need for daily controller therapy. a. Both statements are true. b. Statement I is false, statement II is true. c. Statement I is true, statement II is false. d. Both statements are false. 3. Which of the following statements is true? I. Inhaled corticosteroids (ICS) are effective in reducing wheeze symptoms in preschool children with recurrent wheeze, irrespective of wheeze phenotype (EVW or MTW). II. Adherence to ICS treatment is the main determinant of asthma control in preschool children. a. Both statements are true. b. Statement I is false, statement II is true. c. Statement I is true, statement II is false. d. Both statements are false. 4. Which of the following statements is true? I. Daily controller treatment in preschool children with wheeze reduces the long-term risk of persistent asthma in these children. II. Daily controller therapy in preschool children with wheeze should be viewed as a treatment trial, with scheduled follow-up and tapering down medication to the lowest effective dose. a. Both statements are true. b. Statement I is false, statement II is true. c. Statement I is true, statement II is false. d. Both statements are false. Please find all answers at the back of your handout materials 8 PRESCHOOL WHEEZE: WHAT IS NEW SINCE THE 2008 TASKFORCE? Paul L P Brand Princess Amalia Children’s Centre Isala hospital, Zwolle the Netherlands [email protected] 9 Faculty disclosure • Lecturing, consultancy, travel, and research fees from: – Glaxo Smith Kline – Boehringer Ingelheim – Merck – Thermo Fisher – Nutricia Research – AbbVie 10