Challenges and Limitations of Testing Efficacy of Aerosol Device Delivery in Young Children

Abstract

An increasing number of medical conditions are chronically or acutely managed with some form of aerosolized therapy. Due to the benefit of directly administering medications to the intended site of action, there is great interest in evaluating treatments for aerosol use. One of the major challenges in selecting and testing new drug-device combinations in children is the uncertainty regarding the appropriate outcome measure to choose. In studies involving adult patients, typically exacerbations of disease or airflow obstruction are assessed as endpoints in drug trials or device assessment. However, in young children, choosing endpoints to assess efficacy is difficult due to the potential lack of sensitive, noninvasive endpoints that are easily performed across sites. In this review, we discuss the challenges and limitations of selecting clinical endpoints for drug-device trials in the youngest population, with a focus on novel emerging technologies. This article provides an overview of preschool and infant pulmonary function testing, multiple-breath washout, imaging techniques including computed tomography and magnetic resonance imaging, flexible bronchoscopy in children, mucociliary clearance scans, and exhaled breath condensate.

Optimization and Dose Estimation of Aerosol Delivery to Non-Human Primates

“…(4)(5)(6) Vaccination is mostly performed in children, and this presents particular challenges for efficient pulmonary delivery and dose control. (7,8) This is especially true in very young infants who have low tidal volumes (9) and variable breathing patterns. (10) In addition, small children often do not tolerate aerosol masks, and agitation may cause air leakage at the edges of the facemask.…”