This standardized protocol may prove beneficial in multicenter trials for testing new therapies that are designed to improve MCC/CC.

Our results suggest that nasal deposition of albuterol aerosol generated by a pneumatic nebulizer in 9-month-old infants may be significantly affected by changes in TV, ranging between 50 to 200 mL, whereas total lung deposition may not be affected. These results also predict that environmental losses would be highest when administering to a child breathing at 50 mL TV. These data should be useful to companies who are working to improve aerosol delivery systems to treat infants.

Purpose: To quantify deposition of 99m technetium-labeled powder in the Sophia Anatomical Infant Nose-Throat (SAINT) model of a 9-month old. Methods: Powder was generated by the Solovent (BD Technologies), an active dry powder inhaler with spacer, during 30 seconds of tidal volume (TV) breathing. Activity that passed through the model was captured on a filter and represented powder that was available for deposition in the lungs. Deposition in the nasal cavity, on the filter, and in the spacer was expressed as a percentage of the injected dose into the spacer. Results: Mean (± SD) injected dose averaged 89.5 ± 0.09%, 90.3 ± 0.11%, and 91.3 ± 0.05% at 50, 100, and 200 mL TV, respectively. Mean nasal deposition increased significantly from 50 mL to 100 mL and 200 mL TV with 0.60 ± 0.002%, 1.72 ± 0.007%, and 6.75 ± 07.21%, respectively (all p ≤ 0.05). Similarly, mean filter deposition increased significantly from 50 mL to 100 mL to 200 mL with 0.28 ± 0.00%, 1.14 ± 0.00%, and 3.87 ± 0.01%, respectively (all p < 0.05). Mean retention in the spacer was similar at 50 mL (93.38 ± 0.02%) and at 100 mL TV (89.97 ± 0.04%), but decreased significantly to 71.47 ± 0.05% at 200 mL TV (all p < 0.05). Conclusions: These data suggest for the first time the feasibility of delivering a dry powder formulation to infants and toddlers by actively introducing the powder into a spacer. Lung deposition and nasal deposition, as a percent of injected dose, were dependent on tidal volume with deposition increasing with increasing TV. Nevertheless, deposition, as

BackgroundLittle is known of how mucociliary clearance (MCC) in children with cystic fibrosis (CF) and normal pulmonary function compares with healthy adults, or how an acute inhalation of 7% hypertonic saline (HS) aerosol affects MCC in these same children.MethodsWe compared MCC in 12 children with CF and normal pulmonary function after an acute inhalation of 0.12% saline (placebo), or HS, admixed with the radioisotope 99 mtechnetium sulfur colloid in a double-blind, randomized, cross-over study. Mucociliary clearance on the placebo day in the children was also compared to MCC in 10 healthy, non-CF adults. Mucociliary clearance was quantified over a 90 min period, using gamma scintigraphy, and is reported as MCC at 60 min (MCC60) and 90 min (MCC90).ResultsMedian [interquartile range] MCC60 and MCC90 in the children on the placebo visit were 15.4 [12.4-24.5]% and 19.3 [17.3-27.8%]%, respectively, which were similar to the adults with 17.8 [6.4-28.7]% and 29.6 [16.1-43.5]%, respectively. There was no significant improvement in MCC60 (2.2 [-6.2-11.8]%) or MCC90 (2.3 [-1.2-10.5]%) with HS, compared to placebo. In addition, 5/12 and 4/12 of the children showed a decrease in MCC60 and MCC90, respectively, after inhalation of HS. A post hoc subgroup analysis of the change in MCC90 after HS showed a significantly greater improvement in MCC in children with lower placebo MCC90 compared to those with higher placebo MCC90 (p = 0.045).ConclusionsThese data suggest that percent MCC varies significantly between children with CF lung disease and normal pulmonary functions, with some children demonstrating MCC values within the normal range and others showing MCC values that are below normal values. In addition, although MCC did not improve in all children after inhalation of HS, improvement did occur in children with relatively low MCC values after placebo. This finding suggests that acute inhalation of hypertonic saline may benefit a subset of children with low MCC values.Trial RegistrationClinicalTrials.gov: NCT01293084

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