Performance of PARI eFlow ® To the Editor

I refer to the article with the title “Changes in Performance of the PARI eFlow^® Rapid and PARI LC Plus™ during 6 Months Use by CF Patients” published in September 2009 by Rottier et al. in the Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 22, No. 3, pp. 263–269.

The authors compare the aerosol performance of a tobramycin solution (TOBI) with the PARI LC Plus jet nebulizer and the PARI eFlow^® Rapid, which is a vibrating mesh nebulizer. In their study the nebulizers were assessed in vitro after they had been used for about 6 months by cystic fibrosis (CF) patients. Although the data from used LC Plus nebulizers were compared to previously published data from new LC Plus devices, the eFlow^® Rapid nebulizers were characterized before and after patients used them.

Data in references^(1–8) are in contradiction to those generated by Rottier et al., and it is rather surprising that relevant lung deposition, clinical, and cleaning data on eFlow were fully ignored in the discussion of results. One issue is that specific cleaning and maintenance instructions are required to be followed to assure compliance with the specification of devices during use. Moreover, the article by Bakuridze et al.⁽⁸⁾ “Does repeated disinfection of the eFlow rapid nebulizer affect in vitro performance?” is important, and should have been discussed, because these authors concluded differently in their discussion: “No alteration of the membrane is observed with the steam sterilization procedure up to 60 cycles ( = 2 months of treatment), whatever the antibiotic or the type of water was used.”

Transave Inc. (Monmouth Junction, NJ) is developing a liposomal amikacin formulation (ARIKACE™), and has successfully completed phase II studies in both cystic fibrosis and bronchiectasis. Investigational eFlow nebulizer systems were used in both indications to administer ARIKACE. In selecting the best nebulizer to use with ARIKACE, Transave carefully evaluated different nebulizers with respect to their delivery performance. Crucial to the decision in favor of the eFlow technology was the high Total Output Rate, which corresponds to short nebulization times.⁽⁹⁾

To better understand the durability of eFlow device, we simulated 3 months of ARIKACE therapy with a customized investigational eFlow nebulizer. The nebulizer handsets were cleaned and steam disinfected after each use according to PARI's instruction for use. Additionally, we treated the eFlow's aerosol generator with a commercially available ultrasonic cleaner after each week of simulated use. In addition, the Mass Median Diameter (MMD) and the Delivered Dose (DD) using breath simulation was measured every second week. From these experiments we found no decline in performance of the nebulizer. The time to nebulize 8 mL of ARIKACE remained constant during the entire 3 months of simulated use. Also, the MMD varied within narrow boundaries during the study and DD remained constant. Therefore, we cannot confirm the results of Rottier et al. but agree with those published by Bakuridze et al.⁽⁸⁾

As there are conflicting results published,^(1–8) I would have appreciated a deeper discussion by Rottier et al. of those other results, or at least an acknowledgement that they exist. Transave plans to submit the data from our in vitro simulated-use study to your Journal in the near future. I thank you and the Journal for providing a forum for these thoughtful discussions.