Dosage regimens for inhaled therapy in children should be reconsidered

Abstract

In current asthma guidelines, dosage regimens for inhalation therapy in children are based on adult doses and are generally titrated per kilogram of bodyweight or per square metre of body surface area. However, these recommendations do not correspond well with current knowledge of aerosol therapy in childhood. Lung deposition of the aerosolised drug is the key determinant for clinical efficacy and for systemic side effects of inhalation therapy. Lung deposition increases with age, whereas lung deposition expressed as a percentage per kilogram bodyweight is age-independent. This finding is explained by the self-regulating effect of age-dependent airway anatomy on lung deposition. Therefore, it is more likely that adult doses translate into paediatric doses only by virtue of the differences in self-limiting pulmonary deposition when using the same absolute nominal doses of the medication. Adapting the adult dose to a paediatric dose calculated on body size might be unnecessary and could lead to insufficient pulmonary deposition of medication. These findings suggest that dosage regimens for inhalation therapy for children may have to be reconsidered, and should be determined from dose-ranging studies rather than calculated from adult doses based on body size.

Spacer inhalation technique and deposition of extrafine aerosol in asthmatic children

“…Drug distribution patterns obtained from scintigraphic studies provide information on the effectiveness of aerosol delivery to the lungs and therefore provide an important guide to dosage regimens [32]. The present study has demonstrated that the extrafine formulation shows an even, diffuse deposition throughout the airways.…”

Nanoparticle delivery in infant lungs

“…Though the body mass of growing infants/ children increases continuously after birth (9,12), our data predict that during the same period the deposition efficiency first rapidly increases, then diminishes, peaking around 2 y of age. Based on the arguments above, therefore, dose estimations commonly used in clinical settings (21) may be significantly in error (22,23) and, importantly, may lead to drug doses greatly in excess of targeted levels in infants of~2 y of age.…”

Croup

“…Data derived from use of aerosolised medications in lower-airway disease supports this approach, in that the eff ective dose of drug delivered to the airway is regulated by every individual's tidal volume. [133][134][135][136]…”