Influence of nebulized drugs on ciliary activity in vitro

Introduction : The efficacy of several inhaled drugs is well proven in the treatment of cystic fibrosis (CF). Their use is however extrapolated to other chronic diseases, without clear evidence of benefit. In addition, the influence of inhaled drugs on ciliary activity has not been studied. Objective : To examine the influence of inhaled drugs on ciliary beat frequency (CBF) in an in vitro nebulization model. Isotonic saline (IS), hypertonic saline (HS) and salbutamol (S) were used as neutral, inhibitory and stimulatory control to validate the model. Tobi® (T), Obracin® (O), colistimethate (C) and dornase alpha (D) were the test drugs. Methods : Non CF nasal epithelial cells were cultured as monolayer. On day 4 to 6, confluent cell monolayers were exposed to nebulization in an aerosol chamber for 10 minutes. Images were acquired with a high-speed camera, and CBF was expressed as % of the starting value. CBF until 60 minutes after nebulization was compared between the test condition and IS using mixed model statistics. Per drug, 3 samples of 3 different patients were evaluated on 3 consecutive days. Results : IS did not result in change in CBF. HS resulted in a decrease of CBF to 77% (p 0.021 versus IS), with complete spontaneous recovery at 60 min post nebulization. S resulted in an increase of CBF to 116% (p 0.05). T did not alter CBF (p 0.566), although O caused a decrease of CBF to 59.4% (p 0.0001). C and D respectively caused a small decrease of CBF to 90.7% (NS p 0.085) and increase to 108.5% (p 0.001). Conclusion : Inhaled drugs can influence CBF, due to the product itself, the pH and osmolarity of the solution or to solvents in the solution. This may be relevant to their in vivo efficacy or tolerability.