Dose titration of nebulized budesonide in young children

Abstract

We compared the clinical effect of the glucocorticoid budesonide delivered from two nebulizers Aiolos® and Pari LL® in 38 children less than 4 years of age (mean age, 20.2 months) with chronic wheeze. The design was a controlled, single‐blind, randomized, cross‐over, dose titration study. After a 1‐week run‐in, patients were randomized to treatment with 1 mg budesonide b.i.d. for 2 weeks from either an Aiolos® or a Pari LL® nebulizer. This was followed by a gradual dose reduction period during which the budesonide dose was reduced at 2‐week intervals until unacceptable asthma symptoms appeared or the placebo level was reached. The patient was then switched to budesonide 1 mg b.i.d. from the other nebulizer for 2 weeks, after which the dose was reduced at 2‐week intervals as described for the first period. Patients who completed the study on placebo for 2 weeks without deterioration of their asthma were not included in the statistical analysis. During Period # 1 the minimum effective dose of budesonide was 2 mg/day in 9 patients, 1 mg/day in 10 patients, and 0.5 mg/day in 13 patients. In Period #2 the corresponding figures were 14, 5, and 13 patients. Six patients were excluded after the first period because their asthma control did not deteriorate during dose reduction and when finishing on placebo for 2 weeks. For both nebulizers the reduction in budesonide dose was associated with a small increase in symptoms and use of rescue terbutaline. The mean dose of budesonide delivered to the patient by the Aiolos® was twice as large as that delivered by the Parl LL®: 26% vs. 13% of the nominal dose assessed by the filter method. Nevertheless, no statistically significant difference in clinical effect or mean minimal effective dose (1.1 mg for Aiolos® and 1.2 mg for Pari LL®) could be detected between the two nebulizers. No serious adverse events were observed. We conclude that the minimal effective dose of nebulized budesonide varies from 0.5 to 2.0 mg/day in young children with asthma. A higher drug delivery, as assessed by the filter method, does not necessarily result in better clinical control or lower minimal effective dose. Further studies are needed to assess whether this is due to insufficient sensitivity of the study design in detecting a difference in clinical effect, or whether measurements of drug delivery by the filter method do not reflect lung deposition or clinical effect in young children with wheezing. Pediatr Pulmonol. 1997;23:270–277. © 1997 Wiley‐Liss, Inc.

Does Wearing a Noseclip during Inhalation Improve Lung Deposition?

“…In another study 19 using the filter method, while the delivered-dose differences measured between two types of nebulizers were as large as 100%, no statistically significant difference in clinical effect was observed. The authors point out that drug delivery assessed by the filter method does not necessarily reflect lung deposition and clinical effect because the introduction of an inspiratory filter may result in a somewhat higher resistance.…”

“…The authors point out that drug delivery assessed by the filter method does not necessarily reflect lung deposition and clinical effect because the introduction of an inspiratory filter may result in a somewhat higher resistance. 19,20 Our approach is advantageous as the inhalation system is used in the same way as under routine conditions, so the situation prevailing in practice is accurately reproduced. Wearing the noseclip did not lead under these conditions to the expected increase in the amount deposited into the lungs.…”

Effective Once-Daily Administration of Budesonide Inhalation Suspension by Nebulizer with Facemasks or Mouthpieces for Persistent Asthma in Infants and Young Children

“…(5) Inhaled BIS can be effectively administered to children ,4 years of age, resulting in improved asthma symptom scores. (5,6,(8)(9)(10) A study comparing various methods of albuterol inhalation has demonstrated that as little as 10% of the prescribed dose may reach the lungs with nebulization. (11) Efficiency of inhalation with facemasks, in particular, is compromised by deposition of the drug on the face, in the nose, or outside of the mask.…”

“…12.4 (10) 25.2 In patients able to perform pulmonary function tests consistently; data expressed as the mean change from baseline over the 12-week treatment phase, adjusted for center effect, in this analysis including all patients treated, with the last value carried forward.…”

Drug Delivery from the Turbuhaler and Nebuhaler Pressurized Metered Dose Inhaler to Various Age Groups of Children with Asthma

“…This procedure was performed twice, once with the filter attached during actuation and once when the filter was attached immediately after the actuation. These measurements were not performed with the same pMDI Nebuhalers used in the study, but each had been primed with 15 doses of budesonide the day before the measurement.…”