Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.

Asthma is the most common chronic disease in children. It is characterized by difficulty in breathing and chronic airway inflammation associated with narrowing of the airways, and airway hyperresponsiveness. If left untreated, asthma can lead to respiratory distress and even death. A number of medications are available and prescribed to manage asthma. Yet despite that, only half of the asthmatic patients are able to control their condition. Extracellular vesicles (EVs) play an important role in transporting contents such as nucleic acids, proteins, and lipids to other cells. While EVs have been extensively studied as biomarkers of various pathological states, evidence indicates that they can play protective and therapeutic roles in mitigating diseases such as cancer, cardiovascular disease and asthma. Here we propose to conduct a systematic review that provides a detailed analysis of the therapeutic effect of EVs in mitigating the primary (inflammation, airway hyperresponsiveness) and secondary outcomes (airway remodelling, molecular indices of cellular signalling, and inflammatory mediators in serum) associated with asthma in preclinical studies.