Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1±4 (group I, n=17) and 5±8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber1) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler1 in group I and Volumatic1 in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 mg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean SD) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV).Mean filter dose in group I was 41.7 10.1% for Nebuchamber and 26.0 4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2 9.2% for Nebuchamber and 19.4 7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003).There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5±8 yrs of age. The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age. Eur Respir J 1999; 13: 787±791. Pressurized metered dose inhalers (pMDI) combined with spacers are widely used for the treatment of asthma in children. Although pMDI/spacers are convenient and relatively simple to use, the dose delivery from a spacer depends on a number of patient and device features [1±4]. Predictability and reproducibility of dosing are relevant for any drug therapy. This general pharmacological principle allows the clinician to select the proper dose and device for a given patient. Considerable between-subject variability in aerosol delivery from spacers has been described [1,5]. These results were based on only one or two observations per child in a laboratory setting, recorded within a short interval. Though such studies may provide a good impression of the quality of the different devices, it may not adequately represent the situation in daily life, which is obviously important when prescribing inhaled drugs.One of the factors that can contribute to variability in aerosol delivery is the material from which the spacer is made. Until recently, spacers were made of plastic. Various studies have shown that electro...

We investigated the in vitro influence of breathing patterns on lung dose (LD) and particle size distribution in an infant upper airway cast model in order to determine the optimal particle size for nebulized aerosol delivery to infants. Budesol (nebulizer solution of budesonide) delivery from a perforated vibrating membrane nebulizer (eFlow Baby functional prototype) through an upper airway cast of a nine month old infant (SAINT-model) was measured at a fixed respiratory rate (RR) of 30 breaths per minute (bpm) and a tidal volume (Vt) of 50, 100, and 200 mL, respectively, and at a fixed Vt of 100 mL and a RR of 30, 60, and 78 bpm, respectively. LD expressed as a percentage of the nominal dose (ND; range, 5.8-30.3%) decreased with increasing Vt (p < 0.001) and with increasing RR (p < 0.001). Median mass aerodynamic diameter (MMAD) after passage (range, 2.4-3.4 microm) through the upper airway cast showed a negative correlation with increasing Vt (p < 0.001) and with increasing RR (p = 0.015). Particles available as LD for all simulated breathing pattern showed a particle size distribution with a MMAD of 2.4 microm and a geometric standard deviation (GSD) of 1.56. From our in vitro study, we conclude that the optimal particle size for nebulized aerosols for inhalation therapy for infants should have a MMAD of <2.4 microm.

The term "effectiveness" relates to the question of whether or not a certain treatment works in practice. Usually, such a treatment was first evaluated under tightly controlled conditions in selected patient populations, and the potential benefits were shown. There is, however, a great difference between the efficacy of a given treatment, indicating its optimal therapeutic action in controlled trials, and its effectiveness when applied to a less well-defined population of patients in daily practice. This is especially relevant for asthma in young children, where many factors are responsible for the difference. Among these are, first of all, the heterogeneity of the wheezing phenotype. Other factors include the compliance with prescribed treatments, as determined by the attitude of doctors and parents towards such treatment, the ease of administration and the perceived effects and side effects. Also, the performance of different inhaler devices may be insufficient for a good, reliable dose deposition in young children in daily life. As a result, the current treatment guidelines for preschool children with recurrent wheeze are probably too optimistic in assuming that inhaled treatment is most effective and feasible at all ages. We propose careful re-evaluation of such recommendations in a first-line setting resembling daily life as closely as possible, and consideration of oral treatments as well. Also, we need methods to separate the different phenotypes within the group of recurrently wheezing preschool children to optimize targeting of asthma treatment to those who have ongoing airway inflammation.