Article Text

Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank
  1. Alexander G Mathioudakis1,2,3,
  2. Michael Miligkos4,
  3. Cristina Boccabella5,
  4. Gioulinta S Alimani3,6,
  5. Adnan Custovic7,
  6. A Deschildre8,
  7. Francine Monique Ducharme9,
  8. Omer Kalayci10,
  9. Clare Murray1,2,
  10. Antonio Nieto Garcia11,
  11. Wanda Phipatanakul12,
  12. David Price13,14,
  13. Aziz Sheikh15,
  14. Ioana Octavia Agache16,
  15. Leonard Bacharier17,
  16. Apostolos Beloukas6,18,
  17. Andrew Bentley2,19,
  18. Matteo Bonini5,20,
  19. Jose A Castro-Rodriguez21,
  20. Giuseppe De Carlo22,
  21. Timothy Craig23,
  22. Zuzana Diamant24,25,26,
  23. Wojciech Feleszko27,
  24. Tim Felton1,2,
  25. James E Gern28,
  26. Jonathan Grigg29,
  27. Gunilla Hedlin30,
  28. Elham M Hossny31,
  29. Despo Ierodiakonou32,
  30. Tuomas Jartti33,
  31. Alan Kaplan34,
  32. Robert F Lemanske28,
  33. Peter N Le Souëf35,
  34. Mika J Mäkelä36,
  35. Georgios A Mathioudakis3,
  36. Paolo Matricardi37,
  37. Marina Mitrogiorgou38,
  38. Mario Morais-Almeida39,
  39. Karthik Nagaraju40,
  40. Effie Papageorgiou6,
  41. Helena Pité39,41,42,
  42. Paulo M C Pitrez43,
  43. Petr Pohunek44,
  44. Graham Roberts45,46,47,
  45. Ioanna Tsiligianni32,
  46. Stephen Turner48,
  47. Susanne Vijverberg49,
  48. Tonya A Winders50,
  49. Gary WK Wong51,
  50. Paraskevi Xepapadaki52,
  51. Heather J Zar53,54,
  52. Nikolaos G Papadopoulos1,52
  1. 1Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK
  2. 2North West Lung Centre, Manchester University NHS Foundation Trust, Manchester, UK
  3. 3Athens Breath Centre, Athens, Greece
  4. 4First Department of Pediatrics, "Aghia Sofia" Children's Hospital, University of Athens, Athens, Attica, Greece
  5. 5Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Milano, Lombardia, Italy
  6. 6Department of Biomedical Sciences, University of West Attica, Egaleo, Attica, Greece
  7. 7Department of Paediatrics, Imperial College London, London, UK
  8. 8Unité de Pneumologie et Allergologie Pédiatriques, Hôpital Jeanne de Flandre, CHU Lille, Lille, Hauts-de-France, France
  9. 9Pediatrics, University of Montreal, Montreal, Quebec, Canada
  10. 10Pediatric Allergy and Asthma Unit, Hacettepe Universitesi, Ankara, Turkey
  11. 11Pulmonology and Allergy Unity, La Fe University and Polytechnic Hospital, Valencia, Comunidad Valenciana, Spain
  12. 12Pediatric Allergy and Immunology, Children's Hospital Boston, Boston, Massachusetts, USA
  13. 13Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK
  14. 14Observational and Pragmatic Research Institute, Singapore
  15. 15Asthma UK Centre for Applied Research, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK
  16. 16Allergy and Clinical Immunology, Transylvania University, Brasov, Romania
  17. 17Department of Allergy, Immunology, and Pulmonary Medicine, University of Washington, Seattle, Washington, USA
  18. 18Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
  19. 19Acute Intensive Care Unit, University Hospital of South Manchester NHS Foundation Trust, Manchester, Greater Manchester, UK
  20. 20National Heart and Lung Institute (NHLI), Imperial College London, London, UK
  21. 21Department of Pediatrics, Pontifical Universidad Catolica de Chile, Santiago, Chile
  22. 22Allergy and Airway Diseases Patient's Associations, European Federation of Pharmaceutical Industries and Associations, Brussels, Belgium
  23. 23Allergy, Asthma and Immunology, Penn State University, Hershey, Pennsylvania, USA
  24. 24Department of Respiratory Medicine and Allergology, Institute for Clinical Science, Skane University Hospital Lund Hematological Clinic, Lund, Skåne, Sweden
  25. 25Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
  26. 26Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center of Groningen and QPS-NL, Groningen, Netherlands
  27. 27Department of Pediatric Pulmonology and Allergy, Medical University of Warsaw, Warszawa, Poland
  28. 28Department of Pediatrics and Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
  29. 29Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, London, UK
  30. 30Department of Women's and Children's Health, Karolinska Institute, Stockholm, Stockholm, Sweden
  31. 31Pediatric Allergy and Immunology Unit, Ain Shams University, Cairo, Egypt
  32. 32Department of Social Medicine, Faculty of Medicine, University of Crete, Rethimno, Greece
  33. 33Department of Paediatrics, University of Turku, Turku, Finland
  34. 34Family Physician, Airways Group of Canada, University of Toronto, Toronto, Ontario, Canada
  35. 35School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia
  36. 36Department of Allergy, University of Helsinki, Helsinki, Uusimaa, Finland
  37. 37Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité - University Medicine, Berlin, Germany
  38. 38Third Department of Paediatrics, National and Kapodistrian University of Athens School of Health Sciences, Athens, Greece
  39. 39Allergy Center, Hospital CUF Descobertas, Lisboa, Portugal
  40. 40Allergy & Asthma, VN, Chennai, India
  41. 41Allergy Center, CUF Infante Santo Hospital, Lisbon, Portugal
  42. 42Chronic Diseases Research Center (CEDOC), NOVA Medical School / Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
  43. 43Laboratory of Respiratory Physiology, Infant Center, School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
  44. 44Paediatric Department, Motol University Hospital, Praha, Czech Republic
  45. 45The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport Isle of Wight, UK
  46. 46Faculty of Medicine, Clinical and Experimental Sciences and Human Development in Health Academic Units, University of Southampton, Southampton, UK
  47. 47NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  48. 48Department of Child Health, University of Aberdeen, Aberdeen, Aberdeen, UK
  49. 49Department of Respiratory Medicine and Department of Pediatric Pulmonology, University of Amsterdam, Amsterdam, Netherlands
  50. 50Allergy & Asthma, Global Patient Platform, Virginia, Virginia, USA
  51. 51Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
  52. 52Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Attica, Greece
  53. 53Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, University of Cape Town, Rondebosch, Western Cape, South Africa
  54. 54Unit on Child and Adolescent Health, Medical Reaserch Council, Cape Town, South Africa
  1. Correspondence to Professor Nikolaos G Papadopoulos; ngpallergy{at}


Introduction Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.

Methods and analysis Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.

Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.

Ethics and dissemination Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.

PROSPERO registration numbers CRD42020132990, CRD42020171624.

  • paediatrics
  • asthma
  • paediatric thoracic medicine
  • thoracic medicine

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  • AGM and MM contributed equally.

  • Contributors Study conception: AGM and NGP. Study design: AGM, MM and NGP. Preparation of the manuscript: AGM. Critical revision and final approval of the manuscript: AGM, MM, CB, GSA, AC, AD, FMD, OK, CM, ANG, WP, DP, AS, IOA, LB, AB, AB, MB, JAC-R, GDC, TC, ZD, WF, TF, JEG, JG, GH, EMH, DI, TJ, AK, RFL, PNLS, MJM, GAM, PM, MM, MM-A, KN, EP, HP, PMCP, PP, GR, IT, ST, VS, TAW, GWKW, PX, HJZ and NGP.

  • Funding This work was supported by the Respiratory Effectiveness Group (REG). REG has received support from AstraZeneca, Novartis and Sanofi for continued work on PeARL. (Award/Grant name: PeARL, Award/Grant Number: N/A). This is an investigator initiated study and the funders were not involved in the selection of the topic, or design of these systematic reviews. AGM was supported by the National Institute for Health Research Manchester Biomedical Research Centre (NIHR Manchester BRC).

  • Competing interests AGM reports grants from Boehringer Ingelheim outside the submitted work. AC reports personal fees from Novartis, Regeneron / Sanofi, Thermo Fisher Scientific, Boehringer Ingelheim and Philips, outside the submitted work. LB reports personal fees from Aerocrine, GlaxoSmithKline, Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi/Regeneron, Vectura and Circassia outside the submitted work. TC reports grants and personal fees CSL Behring, Dyax, Takeda, BioCryst, Pharming, personal fees from Grifols, grants and non-financial support from GSK, Regeneron, Novartis/Genetech outside the submitted work. AD reports grants and personal fees from Stallergenes Greer, personal fees from Novartis, ALK, TEVA, GSK, MEDA-MYLAN, CHIESI, AImmune, DBV technologies and Astra Zeneca, outside the submitted work. ZD reports personal fees from academic affiliations, ZD acts as Executive and Scientific Medical Director at a phase I/II pharmacological unit (QPS-NL), which performs clinical studies for pharmaceutical companies. ZD reports personal fees from Astrazeneca, ALK, Aquilon, Boehringer Ingelheim, CSL, HAL Allergy, MSD, and Sanofi-Genzyme outside the submitted work. FMD reports grants from Thorasys; personal fees from Jean-Coutu Pharmaceuticals, unrestricted research funds from Novartis Canada, Teva and Trudell Medical, research grants from GlaxoSmithKline and MEDteq in partnership with Thorasys; honorarium for consultancy work from Covis Pharma and Teva; and honorarium as invited speaker from Covis Pharma, Pharmacy Brunet, outside the submitted work. JEG reports grants from NIH/NIAID, personal fees from Regeneron, Ena Theraputics and MedImmune outside the submitted work; personal fees and stock options from Meissa Vaccines Inc outside the submitted work. JG reports personal fees from GSK, Vifor Pharmaceuticals, Novartis, BV Pharma and AstraZeneca outside the submitted work. AK reports personal fees Astra Zeneca, Behring, Boehringer Ingelheim, Covis, GSK, NovoNordisk, Novartis, Griffols, Pfizer, Sanofi, Teva and Trudel, outside the submitted work. RFL reports grants from NIH, non-financial support from GlaxoSmithKline, Boehringer-Ingelheim, Merck, TEVA, American Academy of Allergy, Asthma and Immunology, grants from Clinical and Translational Science Award (NIH), Childhood Origins of ASThma (COAST) grant, AsthmaNet, personal fees from LSU, Elsevier, UpToDate, the University of Kentucky, ThermoFischer, and Food Allergy Research and Education (FARE) Network, outside the submitted work. CM reports personal fees from Novartis, GSK, Astra Zeneca, Thermo Fisher and Boehringer Ingelheim outside the submitted work. NGP reports personal fees from ALK, Novartis, Nutricia, HAL, Menarini/FAES Farma, Sanofi, Mylan/MEDA, Biomay, AstraZeneca, GSK, MSD, ASIT BIOTECH and Boehringer Ingelheim; grants from Gerolymatos International SA and Capricare outside the submitted work. WP reports grants from NIH; grants and personal fees from Genentech/Novartis, Sanofi/Rgeneron; personal fees GSK; non-financial support from Thermo Fisher, Lincoln Diagnostics, Alk Abello, and Monaghen, outside the submitted work. PP reports grants from Astra Zeneca, Chiesi and TEVA; personal fees from Astra Zeneca, TEVA, Novartis, Mundipharma, S&D Pharma, and GlaxoSmithKline outside the submitted work. DP reports grants from AKL Research and Development, British Lung Foundation, Respiratory Effectiveness Group and the UK National Health Service; grants and personal fees from Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Napp, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, TEVA, Theravance and Zentiva (Sanofi Generics); personal fees from Cipla, GlaxoSmithKline, Kyorin and Merck; non-financial support from Efficacy and Mechanism Evaluation programme, Health Technology Assessment, outside the submitted work; DP also reports stock/stock options from AKL Research and Development which produces phytopharmaceuticals; and owns 74% of the social enterprise Optimum Patient Care (Australia and UK) and 74% of Observational and Pragmatic Research Institute (Singapore), outside the submitted work. GR reports personal fees from ALK, Allergen Therapeutics, Meda Plus, Merck; and a patent for the use of sublingual immunotherapy to prevent the development of allergy in at-risk infants, outside the submitted work. IT reports personal fees from Novartis, GSK, Boehringer Ingelheim and Astra Zeneca; grants from GSK Hellas, outside the submitted work. PX reports personal fees from Nutricia, Nestle, Friesland, Uriach, Novartis Pharma AG, and GlaxoSmithkline outside the submitted work.

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