Severe Asthma in Children and Adolescents: an AWMF Guideline by the German Society for Pediatric Pulmonology

Eckard Hamelmann; Christina Schorlemer; Ernst Eber; Michael Gerstlauer; Andreas Jung; Michael Kabesch; Matthias Volkmar Kopp; Susanne Lau; Christiane Lex; Alex Möller; Bianca Schaub; Nicolaus Schwerk; Thomas Spindler; Christian Taube; Christian Vogelberg; Angela Zacharasiewicz; Stefan Zielen; Antje Schuster; Monika Gappa

doi:10.1055/a-2752-7457

Klin Padiatr
DOI: 10.1055/a-2752-7457

Guidelines

Severe Asthma in Children and Adolescents: an AWMF Guideline by the German Society for Pediatric Pulmonology

Schweres Asthma bei Kindern und Jugendlichen Zusammenfassung der AWMF-Leitlinie koordiniert von der Gesellschaft für Pädiatrische Pneumologie (GPP)

Autor*innen

Eckard Hamelmann

¹Bethel Children Center – Department of Pediatrics, Protestant Hospital Bethel, Bielefeld, Germany (Ringgold ID: RIN39718)

²University Hospital OWL, Bielefeld University, Bielefeld, Germany (Ringgold ID: RIN9167)
Christina Schorlemer

³Bethel Children's Center, Protestant Hospital Bethel, Bielefeld, Germany (Ringgold ID: RIN39718)
Ernst Eber

⁴Paediatrics, Medical University of Graz, Graz, Austria (Ringgold ID: RIN31475)
Michael Gerstlauer

⁵Clinic for children and adolescents, University Hospital Augsburg, Augsburg, Germany (Ringgold ID: RIN39694)
Andreas Jung

⁶Pulmonology, University Children's Hospital Zürich, Zürich, Switzerland (Ringgold ID: RIN30995)
Michael Kabesch

⁷Clinic and Polyclinic for Pediatric and Adolescent Medicine, Barmherzige Brüder Klinik St Hedwig Regensburg, Regensburg, Germany (Ringgold ID: RIN155987)
Matthias Volkmar Kopp

⁸University Clinic for Pediatrics, Inselspital Universitatsspital Bern, Bern, Switzerland (Ringgold ID: RIN27252)
Susanne Lau

⁹Clinic for Pediatrics with a focus on pneumology, immunology, and intensive care medicine, Charité University Hospital Berlin, Berlin, Germany (Ringgold ID: RIN14903)
Christiane Lex

¹⁰Department of Paediatrics and Adolescent Medicine- Paediatric Cardiology, Intensive Care Medicine and Pneumology, University Medical Center Göttingen, Gottingen, Germany (Ringgold ID: RIN84922)
Alex Möller

¹¹Pulmonology, University Children's Hospital Zürich, Zürich, Switzerland (Ringgold ID: RIN30995)
Bianca Schaub

¹²Dr. von Hauner Children's Hospital, LMU Hospital, Munich, Germany (Ringgold ID: RIN27192)
Nicolaus Schwerk

¹³Pediatric pulmonology and neonatology, Hannover Medical School, Hanover, Germany (Ringgold ID: RIN9177)
Thomas Spindler

¹⁴Medical Care Center GmbH, Friedrichshafen Hospital, Friedrichshafen, Germany (Ringgold ID: RIN9228)
Christian Taube

¹⁵Department of Pulmonary Medicine, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
Christian Vogelberg

¹⁶Pediatric Department, University Hospital Carl Gustav Carus, Dresden, Germany (Ringgold ID: RIN39063)
Angela Zacharasiewicz

¹⁷Department of Pediatrics, Vienna Healthcare Group – Campus Ottakring Hospital, Vienna, Austria (Ringgold ID: RIN276212)
Stefan Zielen

¹⁸Institute for Respiratory Diseases, Medaimun GmbH, Frankfurt, Germany
Antje Schuster

¹⁹Center for Pediatric and Adolescent Medicine, University Hospital of Düsseldorf, Düsseldorf, Germany (Ringgold ID: RIN39064)
Monika Gappa

²⁰Pediatrics, Evangelical Hospital Düsseldorf Medical Clinic, Düsseldorf, Germany (Ringgold ID: RIN570653)

Abstract

Background

Asthma is the most common chronic respiratory disease in children and adolescents. While most patients achieve good control with guideline-based treatment, a significant proportion experience persistent symptoms, frequent exacerbations, and impaired quality of life.

Objectives

This guideline aims to define severe and difficult-to-treat asthma in children and adolescents, support diagnostic precision, and provide practical, evidence-based recommendations for assessment and management, including biological therapies.

Materials and methods

The S1 guideline was developed under the coordination of the German Society for Pediatric Pulmonology following AWMF procedures. A structured consensus process involving experts from pediatric pulmonology, allergology, and general pediatrics was conducted. Existing national and international guidelines and new evidence were systematically reviewed and adapted.

Results

Key elements include a stepwise diagnostic algorithm to distinguish difficult-to-treat from truly severe asthma, guidance on assessing adherence, comorbidities, and inflammation biomarkers, and recommendations for targeted biological treatment. This guideline addresses monitoring tools, transition to adult care, and the role of rehabilitation.

Conclusions

Children and adolescents with severe asthma require early referral to specialized centers and a structured, interdisciplinary approach. Personalized treatment strategies—including biologics—should be guided by phenotyping and biomarkers. Registry data are essential to improve care quality and generate real-world evidence.

Zusammenfassung

Hintergrund

Asthma bronchiale ist die häufigste chronische Atemwegserkrankung im Kindes- und Jugendalter. Während der Großteil der Patient:innen unter leitliniengerechter Therapie gut behandelt werden kann, leidet eine relevante Subgruppe an schwerem oder schwer behandelbarem Asthma mit eingeschränkter Lebensqualität und hoher Krankheitslast.

Ziel

Diese S1-Leitlinie zielt darauf ab, schweres Asthma im Kindes- und Jugendalter klar zu definieren, eine strukturierte diagnostische und therapeutische Herangehensweise zu fördern und konkrete Empfehlungen für das Management, einschließlich des Einsatzes von Biologika, zu geben.

Methoden

Die Leitlinie wurde unter Federführung der Gesellschaft für Pädiatrische Pneumologie (GPP) gemäß AWMF-Regelwerk erstellt. Grundlage war ein systematischer Literaturreview relevanter nationaler und internationaler Empfehlungen. Ein multidisziplinäres Expertengremium stimmte alle Empfehlungen konsensbasiert ab.

Ergebnisse

Im Mittelpunkt steht ein mehrstufiges diagnostisches Vorgehen zur Differenzierung zwischen schwer behandelbarem und genuin schwerem Asthma. Es werden Kriterien zur Therapieadhärenz, Komorbiditätserfassung und phänotypspezifischer Auswahl von Biologika dargestellt. Weitere Themen sind Monitoring, Rehabilitation, Transition und zukünftige Therapien. Empfehlungen zur Anwendung bestehender und neuer monoklonaler Antikörper basieren auf aktueller Evidenz.

Schlussfolgerung

Kinder mit schwerem Asthma benötigen eine strukturierte, interdisziplinäre Versorgung. Eine frühe phänotypbasierte Therapie mit Biologika sowie flächendeckende Registerdaten und patientenorientierte Versorgungspfade sind erforderlich, um die Prognose dieser Patientengruppe zu verbessern.

Keywords

Paediatric asthma - severe asthma - biologicals - asthma management - practice guidelines

Schlüsselwörter

Schweres Asthma - Kindliches Asthma - Biologika - Asthmamanagement - Leitlinie

Volltext

Referenzen

References
1 Lommatzsch M, Criée CP, de Jong CCM. et al. S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023 [Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023—published by the German Respiratory Society (DGP) e. V.]. Pneumologie. 2023 Aug; 77(8):461–543. German. doi: 10.1055/a-2070-2135. Epub 2023 Jul 5. Erratum in: Pneumologie 2023; 77 (08) 3 PMID: 37406667
2 Bundesärztekammer (BÄK), Kassenärztliche Bundesvereinigung (KBV), Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) 2024 register. awmf.org/de/leitlinien/detail/nvl-002 [cited: 2025-08-15]
3 Bousquet J, Mantzouranis E, Cruz AA. et al. Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol 2010; 126 (05) 926-938 PMID: 20926125
4 Chung KF, Wenzel SE, Brozek JL. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014; 43 (02) 343-373 Epub 2013 Dec 12
5 Agache I, Akdis CA, Akdis M. et al. EAACI Biologicals Guidelines-Recommendations for severe asthma. Allergy 2021; 76 (01) 14-44 PMID: 32484954 Epub 2020 Aug 10
6 Korn S, Milger K, Skowasch D. et al. The German severe asthma patient: Baseline characteristics of patients in the German Severe Asthma Registry, and relationship with exacerbations and control. Respir Med 2022; 195: 106793 Online ahead of print. PMID: 35248804
7 Eckert JK, Kahle J, Böck A. et al. CHAMP Consortium. CHildhood Allergy and tolerance: Biomarkers and Predictors (CHAMP) and quality of life. Pediatr Allergy Immunol 2022; 33 (01) e13652 PMID: 34396594. Epub 2021 Aug 30
8 Baan EJ, de Roos EW, Engelkes M. et al. Characterization of Asthma by Age of Onset: A Multi-Database Cohort Study. J Allergy Clin Immunol In Practice 2022; 10 (07) 1825-1834 PMID: 35398554
9 Pijnenburg MW, Fleming L. Advances in understanding and reducing the burden of severe asthma in children. Lancet Respir Med 2020; 8 (10) 1032-1044 PMID: 32910897
10 Gaillard EA, Kuehni CE, Turner S. et al. European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5–16 years. Eur Respir J 2021; 58 (05) 2004173
11 Global Initiative for Asthma (GINA). 2022 https://ginasthma.org/wp-content/uploads/2022/07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf
12 Scottish Intercollegiate Guidelines Network (SIGN) / British Thoracic Society (BTS). 2019 https://www.sign.ac.uk/media/1773/sign158-updated.pdf
13 National Institute for Health and Care Excellence. 2017 https://www.nice.org.uk/guidance/ng80/resources/asthma-diagnosis-monitoring-and-chronic-asthma-management-pdf-1837687975621 Last updated: 22 March 2021
14 Pamuk G, Le Bourgeois M, Taam RA. et al. The economic burden of allergic comorbidities in paediatric severe asthma. Pediatr Allergy Immunol 2021; 32 (07) 1559-1565
15 Klimek L, Bachert C, Pfaar O. ARIA guideline 2019: treatment of allergic rhinitis in the German health system. Allergo J Int 2019; 28: 255-276
16 Arasi S, Porcaro F, Cutrera R. et al. Severe asthma and allergy: a paediatric perspective. Front Pediatr 2019; 7: 28
17 Werfel T, Heratizadeh A, Aberer W. et al. Aktualisierung “Systemtherapie bei Neurodermitis” zur S2k-Leitlinie Neurodermitis. JDDG 2021; 19: 151-169
18 Hamelmann E, von Mutius E, Bush A. et al. Adressing the risk domain in the long-term managment of paediatric asthma. Pediatr Allergy Immunol 2020; 31: 233-242
19 Nuttall AG, Beardsmore CS, Gaillard EA. Ventilation heterogeneity in children with severe asthma. Eur J Pediatr 2021; 180 (11) 3399-3404 PMID: 33987684; PMCID: PMC8502735 Epub 2021 May 13
20 Korten I, Zacharasiewicz A, Bittkowski N. et al. Asthma control in children: Body plethysmography in addition to spirometry. Pediatr Pulmonol 2019; 54 (08) 1141-1148
21 Menzies-Gow A, Mansur AH, Brightling CE. Clinical utility of fractional exhaled nitric oxide in severe asthma management. Respir J 2020; 55 (03) 1901633
22 Fielding SS, Pijnenburg MW, de Jongste J. et al. Does treatment guided by exhaled nitric oxide fraction improve outcomes in subgroups of children with asthma?. Eur Respir J 2020; May 21 55 (05) 1901879
23 Turner S, Cotton S, Wood J. et al. Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicentre, parallel, randomised, controlled, phase 3 trial. Lancet Respiratory Med 2022; 10 (06) 584-592
24 Kalm-Stephens P, Malinovschi A, Janson C. et al. Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents. Pediatr Pulmonol 2020; 55 (03) 571-579 Epub 2020 Jan 15
25 Çolak Y, Afzal S, Marott JL. et al. Type-2 inflammation and lung function decline in chronic airway disease in the general population. Thorax 2024; 79 (04) 349-358 PMID: 38195642; PMCID: PMC10958305
26 Bacharier LB, Pavord ID, Maspero JF. et al. Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma. J Allergy Clin Immunol 2024; 154 (01) 101-110 Epub 2024 Jan 23. PMID: 38272375
27 Su MW, Lin WC, Tsai CH. et al. Childhood asthma clusters reveal neutrophil-predominant phenotype with distinct gene expression. Allergy 2018; 73 (10) 2024-2032
28 Fitzpatrick AM, Jackson DJ, Mauger DT. et al. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol 2016; 138 (06) 1608-1618
29 Matsunaga NY, Ribeiro MA, Saad IA. et al. Evaluation of quality of life according to asthma control and asthma severity in children and adolescents. J Bras Pneumol 2015; 41 (06) 502-508
30 Taminskiene V, Alasevicius T, Valiulis A. et al. Quality of life of the family of children with asthma is not related to asthma severity. Eur J Pediatr 2019; 178 (03) 369-376 Epub 2019 Jan 4
31 Fenu G, La Tessa A, Calogero C, Lombardi E. Severe paediatric asthma therapy: Omalizumab-A systematic review and meta-analysis of efficacy and safety profile. Front Pediatr 2023; 10: 1033511
32 Wechsler ME, Ford LB, Maspero JF. et al. Long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma (TRAVERSE): an open-label extension study. Lancet. Respir Med 2022; 10 (01) 11-25
33 Bacharier LB, Maspero JF, Katelaris CH. et al. Liberty Asthma VOYAGE Investigators. Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma. N Engl J Med 2021; 385 (24) 2230-2240 PMID: 34879449
34 Papadopoulos NG, Szefler SJ, Bacharier LB. et al. Assessment of dupilumab in children with moderate-to-severe type 2 asthma with or without evidence of allergic asthma. Allergy 2023; 78 (08) 2157-2167
35 Bacharier LB, Maspero JF, Katelaris CH. et al. Liberty Asthma EXCURSION Investigators. Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study. Lancet Respir Med 2024; 12 (01) 45-54 Epub 2023 Nov 10. PMID: 37956679
36 Jacksen DJ, Bacharier LB, Gergen PJ. et al. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet 2022; 400: 502-511 10351 PMID: 35964610; PMCID: PMC9623810
37 Wetzke M, Funken D, Ahrens FO. et al. Mepolizumab Treatment in Severe Paediatric Asthma: First Multicentric Real-World Data. Klin Padiatr 2022; 234 (05) 305-308
38 Menzies-Gow A, Ponnarambil S, Downie J. et al. DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respir Res 2020; 21 (01) 279 PMID: 33087119; PMCID: PMC7576983
39 Corren Menzies-Gow A, Chupp G. et al. Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. Am J Respir Crit Care Med 2023; 208 (01) 13-24 PMID: 37015033; PMCID: PMC10870853
40 Bleecker E, Blaiss M, Jacob-Nara J. et al. Comparative effectiveness of dupilumab and omalizumab on asthma exacerbations and systemic corticosteroid prescriptions: Real-world US ADVANTAGE study. J Allergy Clin Immunol 2024; 154 (06) 1500-1510 PMID: 39186985 Epub 2024 Aug 24
41 Bloom CI, Franklin C, Bush A. et al. Burden of preschool wheeze and progression to asthma in the UK: Population-based cohort 2007 to 2017. J Allergy Clin Immunol 2021; 147 (05) 1949-1958
42 Beigelman A, Bacharier LB. Management of preschool recurrent wheezing and asthma: a phenotype-based approach. Curr Opin Allergy Clin Immunol 2017; 17 (02) 131-138
43 Fitzpatrick AM, Bacharier LB, Guilbert TW. et al. Phenotypes of Recurrent Wheezing in preschool children: Identification by latent class analysis and utility in prediction of future exacerbation. J Allergy Clin Immunol Pract 2019; 7 (03) 915-924
44 Pauwels RA, Pedersen S, Busse WW. et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003; 361 (9363) 1071-1076
45 Guilbert TW, Morgan WJ, Zeiger RS. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 2006; 354 (19) 1985-1997 PMID: 16687711
46 Kaiser SV, Huynh T, Bacharier LB. et al. Preventing exacerbations in pre-schoolers with recurrent wheeze: A meta-analysis. Paediatrics 2016; 137 (06) e20154496
47 Chauhan BF, Chartrand C, Ni Chroinin M. et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev 2015; Nov 24 2015 (11) CD007949 PMID: 26594816; PMCID: PMC9426997
48 Bersuch E, Gräf F, Renner ED. et al. Lung function improvement and airways inflammation reduction in asthmatic children after a rehabilitation program at moderate altitude. Pediatr Allergy Immunol 2017; 8: 768-775
49 Jung A, Heinrichs I, Geidel C. et al. Inpatient paediatric rehabilitation in chronic respiratory disorders. Paediatr Respir Rev 2012; 13: 123-129
50 Arbeitsgemeinschaft Asthmaschulung im Kindes- und Jugendalter e.V. Qualitätsmanagement in der Asthmaschulung von Kindern und Jugendlichen. iKuh Verlag, 5. Auflage 2018
51 Szczepanski, R. (2017). ABSCHLUSSBERICHT: Erwachsen werden mit ModuS: Fit für den Wechsel – Transitionsmodul im Modularen Schulungsprogramm für chronisch kranke Kinder und Jugendliche. S.7. https://www.bundesgesundheitsministerium.de/fileadmin/Dateien/5_Publikationen/Gesundheit/Berichte/Abschlussbericht_ModuS_Transition_Endf_2018-07-09.pdf22018 (zuletzt aufgerufen am 13.04.2025)
52 Roberts G, Vazquez-Ortis M, Knibb R. et al. EAACI Guidelines on the effective transition of adolescents and young adults with allergy and asthma. Allergy 2020; 75 (11) 2734-2752
53 Wechsler ME, Ruddy MK, Pavord ID. et al. Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. N Engl J Med 2021; 385 (18) 1656-1668 PMID: 34706171
54 Brightling CE, Nair P, Cousins DJ. et al. Risankizumab in Severe Asthma—A Phase 2a, Placebo-Controlled Trial. N Engl J Med 2021; 385 (18) 1669-1679 PMID: 34706172
55 Brightling CE, Gaga M, Inoue H. et al. Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma (LUSTER-1 and LUSTER-2): two phase 3 randomised controlled trials. Lancet Respir Med 2021; 9 (01) 43-56 Epub 2020 Sep 24. PMID: 32979986
56 Cahill KN. Fevipiprant in CRSwNP and comorbid asthma: Wrong target population or wrong PGD2 receptor?. J Allergy Clin Immunol 2022; 149 (05) 1587-1589 Epub 2022 Mar 15. PMID: 35304159
57 Pelaia C, Pelaia G, Crimi C. et al. Novel Biological Therapies for Severe Asthma Endotypes. Biomedicines 2022; 10 (05) 1064 PMID: 35625801; PMCID: PMC9138687