Aerosol Drug Delivery for Infants

INTRODUCTION Every year, approximately 2,500 children are admitted to the pediatric intensive care unit (PICU) at the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center alone [1]. Respiratory illnesses are one of the leading causes of admission [1]. For children with acute respiratory illnesses, inhaled medications are a common method of treatment, as this allows physicians to deliver drugs directly to the patients’ lungs. These treatments are typically delivered via a nebulizer using a face mask or mouthpiece [2]. Once a child is admitted to the PICU, humidified high-flow nasal cannulas are often used to deliver oxygen to the patient or provide airway support, if necessary [3-10]. Since nasal cannulas are regularly used in this setting, they may also provide a logical means of delivering inhaled medications to these patients. Additionally, as infants under the age of 4 months are obligate nose-breathers, delivering aerosols through nasal cannulas is a potential means to improving drug delivery in this cohort compared to the current standard method of delivery (masks) [11]. Despite the potential advantages of this method, using nasal cannulas to deliver inhaled medications in infants provides a variety of challenges. In vivo, the nose is a potential site of significant aerosol deposition, thereby decreasing the amount of drug being delivered to the lungs. Previous studies have shown significant deposition of aerosols in the noses of adults, and we expect this would be even worse for infants due to their smaller airways [12]. Additionally, the small-diameter tubes of a nasal cannula have the potential for significant internal aerosol deposition [13]. Lastly, there are issues with quantifying the dose delivered to the infant’s lungs using nasal cannula devices. In adults, gamma scintigraphy deposition studies have been utilized for determining the percentage of inhaled dose delivered to a patient’s lungs. Until recently, there have been no such studies in infants, due to IRB concerns of using radioisotopes in studies involving infants. Because of this restriction, it has not been possible to validate benchtop models simulating inhaled drug delivery to infants.