Inhaled therapy in very small children (e.g. infants with chronic lung disease of prematurity (CLD)) present particular challenges because breathing patterns are often irregular and tidal volumes and inspiratory flows are low and highly variable (Bisgaard et al, 2002). As a result, the factors that influence drug delivery from holding chambers—such as chamber volume, electrostatic charge, and drug loss through the valve assembly—have a marked impact on drug delivery in neonates. Such holding chambers should therefore have a small volume and a low-resistance inspiratory and expiratory valve system, and should be made of non-electrostatic material.

An ex vivo study (Turpeinen et al, 1999) in 13 infants aged 2–19 months (of these 6 children had been born preterm) showed a high and constant dose delivery from NebuChamber^® in the range of 50–200 mL tidal volumes. A further in vitro study (Janssens et al, 2001) showed that the proportion of an inhaled dose of budesonide delivered from NebuChamber as particles less than 4.7 µm was approximately 12% in infants with a tidal volume of 50 mL (Figure).

NebuChamber also offers the advantage in neonates that only low flow rates are needed to open the inspiratory valves. In an in vitro study (Berg et al, 2002) it was found that the valve could open at flow rates as low as 0.5 litres/minute. Such flow rates can be achieved early in the inspiratory cycle in young children, and even in neonates (Stocks, 1999).

Deposition of budesonide from NebuChamber^® in a model that allows investigation of factors affecting inhaled drug delivery to neonates (Janssens et al, 2001). Note that the decrease in drug delivery seen at higher tidal volumes reflects a higher deposition of drug particles in the nose because of higher inspiratory airflows by older children.

References

Berg E, et al. NebuChamber^® —valve opening at very low inspiratory flow rates. Eur Respir J 2002;20(Suppl 38):172s, Abs 1114.

Bisgaard H, et al. Spacer devices. In: Bisgaard H, O'Callaghan C, Smaldone GC, editor(s). Drug delivery to the lung. New York: Marcel Dekker, 2002:389-420.

Janssens HM, et al. The Sophia Anatomical Infant Nose-Throat (SAINT) model: A valuable tool to study aerosol deposition in infants. J Aerosol Med 2001;14(4):433-41.

Stocks J. Lung function testing in infants. Pediatr Pulmonol Suppl 1999;18:14-20.

Turpeinen M, et al. Metered dose inhaler add-on devices: Is the inhaled mass of drug dependent on the size of the infant? J Aerosol Med 1999;12(3):171-6.