Severe pediatric asthma endotypes: current limits and future perspectives

ABSTRACT

Introduction

Although rare, pediatric severe therapy-resistant asthma (STRA) is a highly heterogeneous, resource-demanding disease that differs significantly from severe adult asthma and whose pathogenesis is still poorly understood.

Areas covered

This review summarizes the latest 10 years of English-written studies defining pediatric STRA endotypes using lung-specific techniques such as bronchoalveolar lavage and endobronchial biopsy. Results of the studies and limits on the field are discussed, together with some future perspectives.

Expert opinion

Over the years, it has become increasingly clear that ’one size does not fit all“ in asthma. However, ”Does an extremely tailored size fit more than one?’. Only using multicentric, longitudinal pediatric studies, will we be able to answer. Three issues could be particularly critical for future research. First, to provide, if existing, a distinction between prepuberal STRA and puberal STRA endotypes to understand the transition from pediatric to adult STRA and to design effective, tailored therapies in adolescents, usually suffering from poorer asthma control. Second, design early treatments for pediatric airway remodeling to preserve lifelong good lung function. Finally, to better characterize inflammation before and during biological therapies, to provide clues on whether to stop or change treatments.

KEYWORDS:

• Bronchoalveolar lavage
• bronchoscopy
• endotypes
• pediatrics
• severe asthma
• severe therapy resistant asthma

Article highlights

• Severe pediatric asthma is a heterogeneous disease with features distinct from severe adult asthma.

• Although invasive and challenging to perform, endobronchial biopsy, bronchoalveolar lavage, and induced sputum provide lung-specific samples that truly picture the airway’s pathology.

• Airway inflammation and airway remodeling are two distinct but mutually supportive pathogenetic mechanisms, which could benefit in the future from specific but synergistic treatments.

• More multicentric, longitudinal, age-specific studies are necessary to design new pediatric targeted therapies.

• Leaky airway epithelium, airway dysbiosis and regulatory cells of the lung microenvironment are promising add-on therapeutic targets in asthma.

• In the future, it is advisable to focus on three main topics: potential early treatments for airway remodeling, severe asthma endotypes among adolescents, and periodic re-endotyping during ongoing biologic therapy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

This work is linked to the research projects: (1) “Integrating deep learning CT‐scan model, biological, and clinical variables to predict severity of asthma in children” (BREATHE, protocol number 0003233/22) supported by the 5 × 1000 funding, Ricerca Corrente, Fondazione IRCCS Policlinico San Matteo; and (2) “Data‐driven forecasting of pediatric asthma endotypes” (DREAMS) promoted under the National Operative Program (NOP) on Research and Innovation 2014–2020 of Italian Ministry of University and Research.

The authors would like to thank the “BREATHE” study group, including academic clinicians and researchers such as Velia Malizia, Giovanna Cilluffo, Salvatore Fasola, Andrea Albarelli, Giuseppe Roberto Marseglia, Giulia Roberto, Giorgia Testa, Lorenzo Preda, and Federica De Matteis for their significant contribution to the research project.

Additional information

Funding

This paper was not funded.