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Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; p = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC (p < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities (p < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC (p < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC (p < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone. [ABSTRACT FROM AUTHOR]