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Lung deposition from the Turbuhaler in children with cystic fibrosis
S G Devadason1, M L Everard, C MacEarlan
1Dept of Respiratory Medicine, Sheffield Children's Hospital, UK.
Insights
The weight-corrected lung dose delivered by Turbuhaler is independent of age in children over six years old. Lower peak inspiratory flow in younger children is offset by their lower body weight, ensuring effective budesonide delivery.
Area of Science:
- Pharmacology
- Pediatrics
- Respiratory Medicine
Background:
- Dry powder inhaler (DPI) drug delivery, like with the Turbuhaler, is influenced by inspiratory flow.
- Clinical use suggests Turbuhaler effectiveness in children, but age-related dose delivery variations remain unclear.
Purpose of the Study:
- To investigate the effect of age on total and weight-corrected budesonide lung dose delivered via Turbuhaler in children.
- To determine the relationship between peak inspiratory flow, age, and drug deposition in the lungs.
Main Methods:
- A deposition study using technetium-99m (99mTc)-labeled budesonide in 21 children (4-16 years) with cystic fibrosis.
- Gamma camera imaging to quantify radiolabel deposition in the lungs versus upper airway and stomach.
- Measurement of peak inspiratory flow (PIF) through the Turbuhaler using a portable spirometer.
Main Results:
- A significant positive correlation was found between PIF and lung dose.
- A significant positive correlation existed between age and total lung dose.
- Weight-corrected lung dose showed a nonsignificant negative correlation with age, suggesting independence in children over six.
Conclusions:
- The weight-corrected lung dose delivered by Turbuhaler is largely independent of age in children over six years.
- Reduced PIF in younger children is compensated by lower body weight, maintaining effective budesonide delivery.
- These findings highlight the flow-dependent characteristics of the Turbuhaler for pediatric drug delivery.
Abstract:
Drug delivery to patients using dry powder inhalers, such as the Turbuhaler, is believed to be influenced by the inspiratory flow used. Clinical studies have indicated that this delivery system can be used effectively by children. However, it is not known how the total and weight-corrected dose delivered to the airways varies with age. A deposition study using technetium-99m (99mTc)-labelled budesonide was performed in order to determine the effect of age on delivery. Twenty one children with cystic fibrosis, aged 4-16 yrs, were recruited. They were clinically stable with normal lung function. Initially, a gamma camera scan was taken in front of a flood source containing 37 MBq of 99mTc. Subsequently, subjects inhaled through a low resistance inspiratory filter connected to a commercially available Turbuhaler. Immediately afterwards they inhaled from a noncommercial Turbuhaler containing budesonide labelled with 99mTc, and then underwent anterior and posterior gamma camera scans. Both Turbuhaler inhalers were attached to a portable spirometer and the peak inspiratory flow through the Turbuhaler was recorded for each inhalation. The total body dose was calculated from the dose deposited on the inspiratory filter connected to the commercial Turbuhaler. Analysis of the gamma camera images provided information on the proportion of the radiolabel delivered to the lungs compared to that deposited in the upper airway and stomach. As expected, a highly significant positive correlation was noted between the peak inspiratory flow generated by the patient through the Turbuhaler and the dose delivered to the lung. Similarly, there was a highly significant positive correlation between age and "total lung dose". However, when total lung dose was corrected for body weight, there was a nonsignificant negative correlation with age. This study suggests that the "weight-corrected lung dose" achieved when children aged > 6 yrs use the Turbuhaler, is largely independent of age. It would appear that the flow-dependent properties of this device are such that the reduced peak inspiratory flow generated by younger children results in a lower dose to the lungs, but that this is off-set by their lower body weight. This is unlikely to be a property of other devices with different flow/drug delivery characteristics.