In vitro determination of the optimal aerosol particle size for inhalation therapy in preterm infants

Background: As inhaled therapy in preterm infants with IRDS (Infant Respiratory Distress Syndrome) or CLD (Chronic Lung Disease) is difficult, the current therapy consists of Surfactant instilled through a tracheal tube or systemic steroids applied orally or intravenously. Current commercially available inhalation devices are not suitable for this age group. New mesh devices able to produce very small particles may allow age specific aerosol therapy and may be applicable even in preterm infants. Objective: This in vitro study assesses the particle size of nebulised aerosols and the distribution in the upper airways and estimates a predicted lung dose for preterm infants. Methods: Budesonide was nebulised through a standard e-Flow device (Pari GmbH, Starnberg, Germany) with two different perforated vibrating membranes (3.5µm and 2.5µm pore diameter) attached to an upper airway model of a 32 weeks gestational age preterm infant by a face mask followed by an NG (New Generation) impactor with 8 sequential compartments simulating the generations of the bronchial tree under various breathing patterns. Particle size distribution as well as lung dose were expressed as a percentage of the total dose and assessed using an HPLC-method. Results: Median mass aerodynamic diameter (MMAD) of particles reaching the lungs was 1.6µm with a geometric standard deviation (GSD) of 1.5. Comparison of the two membranes showed a lung deposition of 17%±1.055 and 23%±1.087 for the greater (3.5µm) and smaller (2.5µm) pores, respectively. Conclusions: The difference between the two membranes is statistically significant (Mann-Whitney-U-Test, p<0.0001). Furthermore, we conclude that aerosols applied to preterm infants of 32 weeks of gestational age should have a MMAD of <1.6µm.