Changes in Performance of the Pari eFlow (R) Rapid and Pari LC Plus (TM) during 6 Months Use by CF Patients

Background: Nebulized antibiotics are important in the treatment of cystic fibrosis. The Pari eFlow (R) rapid with vibrating mesh is often used off-label for the administration of tobramycin (TOBI (R)) because of a reduced nebulization time and easier handling compared to a classic nebulizer-compressor combination. Mesh technology may be vulnerable, however. Therefore, we investigated particle size distribution and output as well as changes in the performance of the eFlow before and after 6 months of use, in comparison with the Pari LC Plus (TM) nebulizer plus Turboboy (TM) compressor. Methods: Size distributions in the aerosols and nebulization times for TOBI were measured with laser diffraction technique; delivered doses by weighing. Results: New eFlows produce considerably larger droplets (X-50 = 3.5 mu m) from TOBI than new LC Plus nebulizers (X-50 = 2.8 mu m). After use, the X-50 increases for both systems (to 3.7 and 3.3 mu m, respectively). The relative span of the size distribution {(X-90-X-10)/X-50} changes from 1.26 to 1.28 mu m for eFlow and from 2.19 to 2.45 mu m for LC Plus. The total nebulization time doubles for LC Plus, whereas in 51% of all experiments the eFlow switched off after 10 min, resulting in incomplete dose delivery. For the eFlow, changes during use are related to clogging of orifices. Once being clogged, only replacement of the mesh restores the original performance. Conclusions: New eFlows produce larger droplets and in a narrower size range compared to new LC Plus nebulizers for TOBI, and therefore both devices are not equivalent. Theoretically a larger portion of the aerosol from eFlow is likely to be deposited in the upper airways. The performance of both tested nebulizers decreases after 6 months of use. For the eFlow, timely replacement of the mesh is necessary. These in vitro results underscore the importance of registration studies of new drug-device combinations.